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Deng S, Xu Y, Warden AR, Xu L, Duan X, He J, Bao K, Xiao R, Azmat M, Hong L, Jiang L, Shen G, Zhang Z, Ding X. Quantitative Proteomics and Metabolomics of Culture Medium from Single Human Embryo Reveal Embryo Quality-Related Multiomics Biomarkers. Anal Chem 2024; 96:11832-11844. [PMID: 38979898 DOI: 10.1021/acs.analchem.4c01494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Abstract
An effective tool to assess embryo quality in the assisted reproduction clinical practice will enhance successful implantation rates and mitigate high risks of multiple pregnancies. Potential biomarkers secreted into culture medium (CM) during embryo development enable rapid and noninvasive methods of assessing embryo quality. However, small volumes, low biomolecule concentrations, and impurity interference collectively preclude the identification of quality-related biomarkers in single blastocyst CM. Here, we developed a noninvasive trace multiomics approach to screen for potential markers in individual human blastocyst CM. We collected 84 CM samples and divided them into high-quality (HQ) and low-quality (LQ) groups. We evaluated the differentially expressed proteins (DEPs) and metabolites (DEMs) in HQ and LQ CM. A total of 504 proteins and 189 metabolites were detected in individual blastocyst CM. Moreover, 9 DEPs and 32 DEMs were identified in different quality embryo CM. We also categorized HQ embryos into positive implantation (PI) and negative implantation (NI) groups based on ultrasound findings on day 28. We identified 41 DEPs and 4 DEMs associated with clinical implantation outcomes in morphologically HQ embryos using a multiomics analysis approach. This study provides a noninvasive multiomics analysis technique and identifies potential biomarkers for clinical embryo developmental quality assessment.
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Affiliation(s)
- Shuxin Deng
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Yuan Xu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Antony R Warden
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Li Xu
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Xiaoqian Duan
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Jie He
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Kaiwen Bao
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Runing Xiao
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Mehmoona Azmat
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Liao Hong
- Department of Clinical Laboratory Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200092, China
| | - Lai Jiang
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Guangxia Shen
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Zhenbo Zhang
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Xianting Ding
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
- State Key Laboratory of Systems Medicine for Cancer, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
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Moustakli E, Zikopoulos A, Skentou C, Stavros S, Sofikitis N, Georgiou I, Zachariou A. Integrative Assessment of Seminal Plasma Biomarkers: A Narrative Review Bridging the Gap between Infertility Research and Clinical Practice. J Clin Med 2024; 13:3147. [PMID: 38892858 PMCID: PMC11173072 DOI: 10.3390/jcm13113147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 06/21/2024] Open
Abstract
Infertility represents a significant global health challenge impacting millions of couples worldwide. Approximately half of all infertile couples exhibit compromised semen quality, indicative of diminished male fertility. While the diagnosis of male infertility traditionally relies on semen analysis, its limitations in providing a comprehensive assessment of male reproductive health have spurred efforts to identify novel biomarkers. Seminal plasma, a complex fluid containing proteins, lipids, and metabolites, has emerged as a rich source of such indicators. Reproduction depends heavily on seminal plasma, the primary transporter of chemicals from male reproductive glands. It provides a non-invasive sample for urogenital diagnostics and has demonstrated potential in the identification of biomarkers linked to illnesses of the male reproductive system. The abundance of seminal proteins has enabled a deeper understanding of their biological functions, origins, and differential expression in various conditions associated with male infertility, including azoospermia, asthenozoospermia, oligozoospermia, teratozoospermia, among others. The true prevalence of male infertility is understated due to the limitations of the current diagnostic techniques. This review critically evaluates the current landscape of seminal plasma biomarkers and their utility in assessing male infertility. Βy bridging the gap between research and clinical practice, the integrative assessment of seminal plasma biomarkers offers a multimodal approach to comprehensively evaluate male infertility.
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Affiliation(s)
- Efthalia Moustakli
- Laboratory of Medical Genetics, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece;
| | - Athanasios Zikopoulos
- Obstetrics and Gynecology, Royal Devon and Exeter Hospital, Barrack Rd, Exeter EX 25 DW, UK;
| | - Charikleia Skentou
- Department of Obstetrics and Gynecology, Medical School of Ioannina, University General Hospital, 45110 Ioannina, Greece;
| | - Sofoklis Stavros
- Third Department of Obstetrics and Gynecology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Nikolaos Sofikitis
- Department of Urology, School of Medicine, Ioannina University, 45110 Ioannina, Greece; (N.S.); (A.Z.)
| | - Ioannis Georgiou
- Laboratory of Medical Genetics, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece;
| | - Athanasios Zachariou
- Department of Urology, School of Medicine, Ioannina University, 45110 Ioannina, Greece; (N.S.); (A.Z.)
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Feng F, Huang C, Luosang D, Ma X, La Y, Wu X, Guo X, Pingcuo Z, Liang C. Serum Metabolomic Analysis of Synchronous Estrus in Yaks Based on UPLC-Q-TOF MS Technology. Animals (Basel) 2024; 14:1399. [PMID: 38791618 PMCID: PMC11117382 DOI: 10.3390/ani14101399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 04/21/2024] [Accepted: 05/01/2024] [Indexed: 05/26/2024] Open
Abstract
The yak is a unique species of livestock found in the Qinghai-Tibet Plateau and its surrounding areas. Due to factors such as late sexual maturity and a low rate of estrus, its reproductive efficiency is relatively low. The process of estrus synchronization in yaks plays a crucial role in enhancing their reproductive success and ensuring the continuation of their species. In order to clarify the characteristics of the serum metabolites of yak estrus synchronization, the yaks with inactive ovaries were compared with the estrus synchronization yaks. In this study, yaks were divided into the inactive ovaries group (IO), gonarelin-induced yak estrus group (GnRH), and chloprostenol sodium-induced yak estrus group (PGF). After the completion of the estrus synchronization treatment, blood samples were collected from the jugular veins of the non-estrus yaks in the control group and the yaks with obvious estrus characteristics in the GnRH and PGF groups. Metabolites were detected by ultra-high performance liquid chromatography-mass spectrometry, and differential metabolites were screened by multivariate statistical analysis. The results showed that a total of 70 significant differential metabolites were screened and identified in the GnRH vs. IO group, and 77 significant differential metabolites were screened and identified in the PGF vs. IO group. Compared with non-estrus yaks, 36 common significant differential metabolites were screened out after the induction of yak estrus by gonarelin (GnRH) and cloprostenol sodium (PGF), which were significantly enriched in signaling pathways such as the beta oxidation of very long chain fatty acids, bile acid biosynthesis, oxidation of branched chain fatty acids, steroidogenesis, steroid biosynthesis, and arginine and proline metabolism. This study analyzed the effects of gonadotropin releasing hormone (GnRH) and prostaglandin F (PGF) on the reproductive performance of yaks treated with estrus synchronization, which provides a theoretical basis for the optimization and application of yak estrus synchronization technology and promotes the healthy development of the yak industry.
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Affiliation(s)
- Fen Feng
- Key Laboratory of Yak Breeding of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (F.F.); (C.H.); (X.M.); (Y.L.); (X.W.); (X.G.)
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
| | - Chun Huang
- Key Laboratory of Yak Breeding of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (F.F.); (C.H.); (X.M.); (Y.L.); (X.W.); (X.G.)
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
| | - Dunzhu Luosang
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Sciences, Lasa 850004, China;
| | - Xiaoming Ma
- Key Laboratory of Yak Breeding of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (F.F.); (C.H.); (X.M.); (Y.L.); (X.W.); (X.G.)
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
| | - Yongfu La
- Key Laboratory of Yak Breeding of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (F.F.); (C.H.); (X.M.); (Y.L.); (X.W.); (X.G.)
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
| | - Xiaoyun Wu
- Key Laboratory of Yak Breeding of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (F.F.); (C.H.); (X.M.); (Y.L.); (X.W.); (X.G.)
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
| | - Xian Guo
- Key Laboratory of Yak Breeding of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (F.F.); (C.H.); (X.M.); (Y.L.); (X.W.); (X.G.)
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
| | - Zhandui Pingcuo
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Sciences, Lasa 850004, China;
| | - Chunnian Liang
- Key Laboratory of Yak Breeding of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (F.F.); (C.H.); (X.M.); (Y.L.); (X.W.); (X.G.)
- Plateau Agricultural Science and Technology Innovation Center, Lasa 850004, China
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Tvrdonova K, Belaskova S, Rumpikova T, Rumpik D, Myslivcova Fucikova A, Malir F. Prediction of live birth - selection of embryos using morphokinetic parameters. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2024; 168:74-80. [PMID: 36622075 DOI: 10.5507/bp.2022.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2022] Open
Abstract
BACKROUND The goal of assisted reproduction is for a couple treated with IVF techniques to end the treatment by giving birth to a healthy baby. A neccessary presumption for success is the identification of the best embryo with high implantation and developmental potential. One option is to select an euploid embryo by invasive preimplantaion genetic testing for aneuploidy (PGT-A) or it is possible to select the best embryo by non-invasive time-lapse monitoring (TLM), specifically based on morphokinetic parameters and morphological markers that are able to identify an embryo with high developmental potential. MATERIALS AND METHODS The study involved a total of 1060 embryos (585 euploid and 475 aneuploid embryos after PGT-A) with good morphology from 329 patients in the period 01/2016-10/2021. All embryos were cultured in a time-lapse incubator, trophectoderm (TE) cells biopsies for PGT-A examination were performed on day 5 (D5) or day 6 (D6) of culture. During the study period, 225 frozen embryo transfers (FET) of one euploid embryo were performed. Based on the treatment outcome, the embryos were divided into 2 groups - euploid embryos, which led to the birth of a healthy child, and euploid embryos that did not show fetal heartbeat (FHB) after FET. RESULTS Based on the statistical analysis of the embryos without implantation and the embryos with live birth, it is clear that the morphokinetic parameters t5 (time of division into 5 cells) and tSB (time of start of blastulation) are significantly different. CONCLUSION The results suggest that of the morphokinetic parameters tSB and t5 are predictive indicators for selecting an embryo with high developmental potential and with a high probability of achieving the birth of a healthy child.
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Affiliation(s)
- Katerina Tvrdonova
- Department of Biology, Faculty of Sciences, University Hradec Kralove, 500 03 Hradec Kralove, Czech Republic
- Clinic of Reproductive Medicine and Gynecology Zlin, U Lomu 638, 760 01 Zlin, Czech Republic
| | - Silvie Belaskova
- Institute of Mathematics and Statistics, Faculty of Science, Masaryk University, 611 37 Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
| | - Tatana Rumpikova
- Clinic of Reproductive Medicine and Gynecology Zlin, U Lomu 638, 760 01 Zlin, Czech Republic
| | - David Rumpik
- Clinic of Reproductive Medicine and Gynecology Zlin, U Lomu 638, 760 01 Zlin, Czech Republic
| | - Alena Myslivcova Fucikova
- Department of Biology, Faculty of Sciences, University Hradec Kralove, 500 03 Hradec Kralove, Czech Republic
| | - Frantisek Malir
- Department of Biology, Faculty of Sciences, University Hradec Kralove, 500 03 Hradec Kralove, Czech Republic
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Gao J, Xiao Y. Metabolomics and its applications in assisted reproductive technology. IET Nanobiotechnol 2023. [PMID: 37248807 PMCID: PMC10374554 DOI: 10.1049/nbt2.12141] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/19/2023] [Accepted: 04/01/2023] [Indexed: 05/31/2023] Open
Abstract
Metabolomics, an emerging omics technology developed in the post-gene age, is an important part of systems biology. It interprets the pathophysiological state of the subject by quantitatively describing the dynamic changes of metabolites through analytical methods, mainly mass spectrometry (MS) and nuclear magnetic resonance (NMR). Assisted reproductive technology (ART) is a method used to manipulate sperm, oocytes, and embryos to achieve conception. Recently, several studies have reported that metabolomics methods can be used to measure metabolites in ART samples; these metabolites can be used to evaluate the quality of gametes and embryos. This article reviews the progress of research on metabolomics and the application of this technology in the field of ART, thus providing a reference for research and development directions in the future.
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Affiliation(s)
- Jingying Gao
- Wuxi No.2 People's Hospital, Jiangnan University Medical Center, Wuxi, Jiangsu, China
| | - Yan Xiao
- Wuxi No.2 People's Hospital, Jiangnan University Medical Center, Wuxi, Jiangsu, China
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de Oliveira Fernandes G, de Lima CB, Fidelis AAG, Milazzotto MP, Dode MAN. Metabolic signature of spent culture media shows lipid metabolism as a determinant of pregnancy outcomes. Reprod Domest Anim 2023; 58:117-128. [PMID: 36156318 DOI: 10.1111/rda.14271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 09/11/2022] [Accepted: 09/23/2022] [Indexed: 01/07/2023]
Abstract
In the present study, we investigated the spent culture media of in vitro produced (IVP) bovine embryos which did (group Pregnant) or did not (group Non-pregnant) establish pregnancy after transfer. For that purpose, IVP embryos on D5 were transferred to individual droplets for the last 48 h of culture. Embryos at the blastocyst stage were then transferred to synchronized recipients, while respective culture media drops were collected and evaluated individually. The list of metabolites present in spent culture media was obtained by electrospray ionization mass spectrometry (ESI-MS) and analysed with Metaboanalyst® to characterize the metabolic profile of each group. The spectrometric analysis showed that pathways related to lipid metabolism, particularly fatty acids degradation via beta-oxidation, were more present in the Pregnant group whereas no significant pathway was identified in the group Non-pregnant. By using this method, we were able to identify a metabolic signature in culture media that allows for a better comprehension of preferential metabolic routes taken by the most viable embryos. These findings offer great insights into the biochemistry of embryo development and reveal a potential target for the development of better-quality IVP systems, as well as tools to identify bovine embryos with greater chances to establish and maintain pregnancy.
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Affiliation(s)
| | - Camila Bruna de Lima
- Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle (CRDSI), Département des Sciences Animales, Faculté des Sciences de l'Agriculture et de l'Alimentation, Université Laval, Québec, Canada.,Laboratory of Embryonic Metabolism and Epigenetic, Center of Natural and Human Science, Federal University of ABC, Santo Andre, Brazil
| | | | - Marcella Pecora Milazzotto
- Laboratory of Embryonic Metabolism and Epigenetic, Center of Natural and Human Science, Federal University of ABC, Santo Andre, Brazil
| | - Margot Alves Nunes Dode
- School of Agriculture and Veterinary Medicine, University of Brasilia, Brasília, Brazil.,Embrapa Genetic Resources and Biotechnology, Laboratory of Animal Reproduction, Brasília, Brazil
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Kim J, Lee J, Jun JH. Non-invasive evaluation of embryo quality for the selection of transferable embryos in human in vitro fertilization-embryo transfer. Clin Exp Reprod Med 2022; 49:225-238. [PMID: 36482497 PMCID: PMC9732075 DOI: 10.5653/cerm.2022.05575] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 07/28/2023] Open
Abstract
The ultimate goal of human assisted reproductive technology is to achieve a healthy pregnancy and birth, ideally from the selection and transfer of a single competent embryo. Recently, techniques for efficiently evaluating the state and quality of preimplantation embryos using time-lapse imaging systems have been applied. Artificial intelligence programs based on deep learning technology and big data analysis of time-lapse monitoring system during in vitro culture of preimplantation embryos have also been rapidly developed. In addition, several molecular markers of the secretome have been successfully analyzed in spent embryo culture media, which could easily be obtained during in vitro embryo culture. It is also possible to analyze small amounts of cell-free nucleic acids, mitochondrial nucleic acids, miRNA, and long non-coding RNA derived from embryos using real-time polymerase chain reaction (PCR) or digital PCR, as well as next-generation sequencing. Various efforts are being made to use non-invasive evaluation of embryo quality (NiEEQ) to select the embryo with the best developmental competence. However, each NiEEQ method has some limitations that should be evaluated case by case. Therefore, an integrated analysis strategy fusing several NiEEQ methods should be urgently developed and confirmed by proper clinical trials.
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Affiliation(s)
- Jihyun Kim
- Department of Obstetrics and Gynaecology, Seoul Medical Center, Seoul, Republic of Korea
| | - Jaewang Lee
- Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Seongnam, Republic of Korea
| | - Jin Hyun Jun
- Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Seongnam, Republic of Korea
- Department of Senior Healthcare, Graduate School, Eulji University, Seongnam, Republic of Korea
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Kakourou G, Mamas T, Vrettou C, Traeger-Synodinos J. An Update on Non-invasive Approaches for Genetic Testing of the Preimplantation Embryo. Curr Genomics 2022; 23:337-352. [PMID: 36778192 PMCID: PMC9878856 DOI: 10.2174/1389202923666220927111158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 08/29/2022] [Accepted: 09/06/2022] [Indexed: 11/22/2022] Open
Abstract
Preimplantation Genetic Testing (PGT) aims to reduce the chance of an affected pregnancy or improve success in an assisted reproduction cycle. Since the first established pregnancies in 1990, methodological approaches have greatly evolved, combined with significant advances in the embryological laboratory. The application of preimplantation testing has expanded, while the accuracy and reliability of monogenic and chromosomal analysis have improved. The procedure traditionally employs an invasive approach to assess the nucleic acid content of embryos. All biopsy procedures require high technical skill, and costly equipment, and may impact both the accuracy of genetic testing and embryo viability. To overcome these limitations, many researchers have focused on the analysis of cell-free DNA (cfDNA) at the preimplantation stage, sampled either from the blastocoel or embryo culture media, to determine the genetic status of the embryo non-invasively. Studies have assessed the origin of cfDNA and its application in non-invasive testing for monogenic disease and chromosomal aneuploidies. Herein, we discuss the state-of-the-art for modern non-invasive embryonic genetic material assessment in the context of PGT. The results are difficult to integrate due to numerous methodological differences between the studies, while further work is required to assess the suitability of cfDNA analysis for clinical application.
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Affiliation(s)
- Georgia Kakourou
- Laboratory of Medical Genetics, National and Kapodistrian University of Athens, St. Sophia's Children's Hospital, 11527, Athens, Greece,Address correspondence to this author at the Laboratory of Medical Genetics, National and Kapodistrian University of Athens, St. Sophia's Children's Hospital, 11527, Athens, Greece; Tel/Fax: +302107467467; E-mail:
| | - Thalia Mamas
- Laboratory of Medical Genetics, National and Kapodistrian University of Athens, St. Sophia's Children's Hospital, 11527, Athens, Greece
| | - Christina Vrettou
- Laboratory of Medical Genetics, National and Kapodistrian University of Athens, St. Sophia's Children's Hospital, 11527, Athens, Greece
| | - Joanne Traeger-Synodinos
- Laboratory of Medical Genetics, National and Kapodistrian University of Athens, St. Sophia's Children's Hospital, 11527, Athens, Greece
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Zhu L, Zhou T, Iyyappan R, Ming H, Dvoran M, Wang Y, Chen Q, Roberts RM, Susor A, Jiang Z. High-resolution ribosome profiling reveals translational selectivity for transcripts in bovine preimplantation embryo development. Development 2022; 149:280468. [PMID: 36227586 PMCID: PMC9687001 DOI: 10.1242/dev.200819] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 09/26/2022] [Indexed: 11/06/2022]
Abstract
High-resolution ribosome fractionation and low-input ribosome profiling of bovine oocytes and preimplantation embryos has enabled us to define the translational landscapes of early embryo development at an unprecedented level. We analyzed the transcriptome and the polysome- and non-polysome-bound RNA profiles of bovine oocytes (germinal vesicle and metaphase II stages) and early embryos at the two-cell, eight-cell, morula and blastocyst stages, and revealed four modes of translational selectivity: (1) selective translation of non-abundant mRNAs; (2) active, but modest translation of a selection of highly expressed mRNAs; (3) translationally suppressed abundant to moderately abundant mRNAs; and (4) mRNAs associated specifically with monosomes. A strong translational selection of low-abundance transcripts involved in metabolic pathways and lysosomes was found throughout bovine embryonic development. Notably, genes involved in mitochondrial function were prioritized for translation. We found that translation largely reflected transcription in oocytes and two-cell embryos, but observed a marked shift in the translational control in eight-cell embryos that was associated with the main phase of embryonic genome activation. Subsequently, transcription and translation become more synchronized in morulae and blastocysts. Taken together, these data reveal a unique spatiotemporal translational regulation that accompanies bovine preimplantation development.
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Affiliation(s)
- Linkai Zhu
- School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Tong Zhou
- Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557-0352, USA
| | - Rajan Iyyappan
- Laboratory of Biochemistry and Molecular Biology of Germ Cells, Institute of Animal Physiology and Genetics, CAS, 277 21 Liběchov, Czech Republic
| | - Hao Ming
- School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Michal Dvoran
- Laboratory of Biochemistry and Molecular Biology of Germ Cells, Institute of Animal Physiology and Genetics, CAS, 277 21 Liběchov, Czech Republic
| | - Yinjuan Wang
- School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Qi Chen
- Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA
| | - R Michael Roberts
- Department of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211-7310, USA
| | - Andrej Susor
- Laboratory of Biochemistry and Molecular Biology of Germ Cells, Institute of Animal Physiology and Genetics, CAS, 277 21 Liběchov, Czech Republic
| | - Zongliang Jiang
- School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA 70803, USA
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Xu M, Wu W, Zhao M, Chung JPW, Li TC, Chan DYL. Common dysmorphic oocytes and embryos in assisted reproductive technology laboratory in association with gene alternations. Int J Biochem Cell Biol 2022; 152:106298. [PMID: 36122887 DOI: 10.1016/j.biocel.2022.106298] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 09/13/2022] [Accepted: 09/14/2022] [Indexed: 11/29/2022]
Abstract
Amorphic or defected oocytes and embryos are commonly observed in assisted reproductive technology (ART) laboratories. It is believed that a proper gene expression at each stage of embryo development contributes to the possibility of a decent-quality embryo leading to successful implantation. Many studies reported that several defects in embryo morphology are associated with gene expressions during in vitro fertilization (IVF) treatment. There is lacking literature review on summarizing common morphological defects about gene alternations. In this review, we summarized the current literature. We selected 64 genes that have been reported to be involved in embryo morphological abnormalities in animals and humans, 30 of which were identified in humans and might be the causes of embryonic changes. Five papers focusing on associations of multiple gene expressions and embryo abnormalities using RNA transcriptomes were also included during the search. We have also reviewed our time-lapse image database with over 3000 oocytes/embryos to show morphological defects possibly related to gene alternations reported previously in the literature. This holistic review can better understand the associations between gene alternations and morphological changes. It is also beneficial to select important biomarkers with strong evidence in IVF practice and reveal their potential application in embryo selection. Also, identifying genes may help patients with genetic disorders avoid unnecessary treatments by providing preimplantation genetic testing for monogenic/single gene defects (PGT-M), reduce embryo replacements by less potential, and help scientists develop new methods for oocyte/embryo research in the near future.
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Affiliation(s)
- Murong Xu
- Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Waner Wu
- Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Mingpeng Zhao
- Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Reproductive Medicine, Department of Obstetrics and Gynaecology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jacqueline Pui Wah Chung
- Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Tin Chiu Li
- Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - David Yiu Leung Chan
- Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
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11
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Lechniak D, Sell-Kubiak E, Warzych E. The metabolic profile of bovine blastocysts is affected by in vitro culture system and the pattern of first zygotic cleavage. Theriogenology 2022; 188:43-51. [DOI: 10.1016/j.theriogenology.2022.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 05/25/2022] [Accepted: 05/25/2022] [Indexed: 11/27/2022]
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12
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LC-MS Analysis Revealed the Significantly Different Metabolic Profiles in Spent Culture Media of Human Embryos with Distinct Morphology, Karyotype and Implantation Outcomes. Int J Mol Sci 2022; 23:ijms23052706. [PMID: 35269848 PMCID: PMC8911215 DOI: 10.3390/ijms23052706] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/17/2022] [Accepted: 02/25/2022] [Indexed: 12/10/2022] Open
Abstract
In this study we evaluated possible differences in metabolomic profiles of spent embryo culture media (SECM) of human embryos with distinct morphology, karyotype, and implantation outcomes. A total of 153 samples from embryos of patients undergoing in vitro fertilization (IVF) programs were collected and analyzed by HPLC-MS. Metabolomic profiling and statistical analysis revealed clear clustering of day five SECM from embryos with different morphological classes and karyotype. Profiling of day five SECM from embryos with different implantation outcomes showed 241 significantly changed molecular ions in SECM of successfully implanted embryos. Separate analysis of paired SECM samples on days three and five revealed 46 and 29 molecular signatures respectively, significantly differing in culture media of embryos with a successful outcome. Pathway enrichment analysis suggests certain amino acids, vitamins, and lipid metabolic pathways to be crucial for embryo implantation. Differences between embryos with distinct implantation potential are detectable on the third and fifth day of cultivation that may allow the application of culture medium analysis in different transfer protocols for both fresh and cryopreserved embryos. A combination of traditional morphological criteria with metabolic profiling of SECM may increase implantation rates in assisted reproductive technology programs as well as improve our knowledge of the human embryo metabolism in the early stages of development.
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13
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Milazzotto MP, Noonan MJ, de Almeida Monteiro Melo Ferraz M. Mining RNAseq data reveals dynamic metaboloepigenetic profiles in human, mouse and bovine pre-implantation embryos. iScience 2022; 25:103904. [PMID: 35252810 PMCID: PMC8889150 DOI: 10.1016/j.isci.2022.103904] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/20/2021] [Accepted: 02/07/2022] [Indexed: 12/01/2022] Open
Abstract
Metaboloepigenetic regulation has been reported in stem cells, germ cells, and tumor cells. Embryonic metaboloepigenetics, however, have just begun to be described. Here we analyzed RNAseq data to characterize the metaboloepigenetic profiles of human, mouse, and bovine pre-implantation embryos. In embryos, metaboloepigenetic reprogramming was species-specific, varied with the developmental stage and was disrupted with in vitro culture. Metabolic pathways and gene expressions were strongly correlated with early embryo DNA methylation and were changed with in vitro culture. Although the idea that the in vitro environment may influence development is not new, there has been little progress on improving pregnancy rates after decades using in vitro fertilization. Hence, the present data will contribute to understanding how the in vitro manipulation affects the metaboloepigenetic status of early embryos, which can be used to establish culture strategies aimed at improving the in vitro environment and, consequently, pregnancy rates and offspring health.
Embryonic metaboloepigenetic reprogramming is stage- and species-specific In vitro culture disrupts the in vivo embryonic metaboloepigenetic reprogramming Metabolic genes and pathways are highly correlated with embryo methylome
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Affiliation(s)
- Marcella Pecora Milazzotto
- Center of Natural and Human Sciences, Federal University of ABC, São Paulo, 09210-580 Santo André, Brazil
| | - Michael James Noonan
- The Irving K. Barber School of Sciences, The University of British Columbia, Okanagan Campus, Kelowna, BC V1V 1V7, Canada
| | - Marcia de Almeida Monteiro Melo Ferraz
- Gene Center Munich, Ludwig-Maximilians University of Munich, 80539 Munich, Germany
- Clinic of Ruminants, Faculty of Veterinary Medicine Ludwig-Maximilians University of Munich, 80539 Munich, Germany
- Corresponding author
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14
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Salmerón AM, Tristán AI, Abreu AC, Fernández I. Serum Colorectal Cancer Biomarkers Unraveled by NMR Metabolomics: Past, Present, and Future. Anal Chem 2022; 94:417-430. [PMID: 34806875 PMCID: PMC8756394 DOI: 10.1021/acs.analchem.1c04360] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Ana M. Salmerón
- Department of Chemistry and
Physics, Research Centre CIAIMBITAL, University
of Almería, Ctra. Sacramento, s/n, 04120 Almería, Spain
| | - Ana I. Tristán
- Department of Chemistry and
Physics, Research Centre CIAIMBITAL, University
of Almería, Ctra. Sacramento, s/n, 04120 Almería, Spain
| | - Ana C. Abreu
- Department of Chemistry and
Physics, Research Centre CIAIMBITAL, University
of Almería, Ctra. Sacramento, s/n, 04120 Almería, Spain
| | - Ignacio Fernández
- Department of Chemistry and
Physics, Research Centre CIAIMBITAL, University
of Almería, Ctra. Sacramento, s/n, 04120 Almería, Spain
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15
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Plaza-Florido A, Pérez-Prieto I, Molina-Garcia P, Radom-Aizik S, Ortega FB, Altmäe S. Transcriptional and Epigenetic Response to Sedentary Behavior and Physical Activity in Children and Adolescents: A Systematic Review. Front Pediatr 2022; 10:917152. [PMID: 35813370 PMCID: PMC9263076 DOI: 10.3389/fped.2022.917152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/02/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are poorly understood. We aimed to synthesize the current knowledge of the association of sedentary behavior and physical activity (acute and chronic effects) with gene expression and epigenetic modifications in children and adolescents. METHODS PubMed, Web of Science, and Scopus databases were systematically searched until April 2022. A total of 15 articles were eligible for this review. The risk of bias assessment was performed using the Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews and/or a modified version of the Downs and Black checklist. RESULTS Thirteen studies used candidate gene approach, while only 2 studies performed high-throughput analyses. The candidate genes significantly linked to sedentary behavior or physical activity were: FOXP3, HSD11B2, IL-10, TNF-α, ADRB2, VEGF, HSP70, SOX, and GPX. Non-coding Ribonucleic acids (RNAs) regulated by sedentary behavior or physical activity were: miRNA-222, miRNA-146a, miRNA-16, miRNA-126, miR-320a, and long non-coding RNA MALAT1. These molecules are involved in inflammation, immune function, angiogenic process, and cardiovascular disease. Transcriptomics analyses detected thousands of genes that were altered following an acute bout of physical activity and are linked to gene pathways related to immune function, apoptosis, and metabolic diseases. CONCLUSION The evidence found to date is rather limited. Multidisciplinary studies are essential to characterize the molecular mechanisms in response to sedentary behavior and physical activity in the pediatric population. Larger cohorts and randomized controlled trials, in combination with multi-omics analyses, may provide the necessary data to bring the field forward. SYSTEMATIC REVIEW REGISTRATION [www.ClinicalTrials.gov], identifier [CRD42021235431].
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Affiliation(s)
- Abel Plaza-Florido
- Department of Physical and Sports Education, Faculty of Sport Sciences, PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain
| | - Inmaculada Pérez-Prieto
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Granada, Spain.,Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain
| | - Pablo Molina-Garcia
- Department of Physical and Sports Education, Faculty of Sport Sciences, PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.,Instituto de Investigación Biosanitaria (ibs.Granada), Physical Medicine and Rehabilitation Service, Virgen de las Nieves University Hospital, Granada, Spain
| | - Shlomit Radom-Aizik
- Pediatric Exercise and Genomics Research Center, UC Irvine School of Medicine, Irvine, CA, United States
| | - Francisco B Ortega
- Department of Physical and Sports Education, Faculty of Sport Sciences, PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.,Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.,Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
| | - Signe Altmäe
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Granada, Spain.,Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain.,Division of Obstetrics and Gynecology, CLINTEC, Karolinska Institutet, Stockholm, Sweden.,Competence Centre on Health Technologies, Tartu, Estonia
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16
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Li J, Li C, Liu X, Yang J, Zhang Q, Han W, Huang G. GDF9 concentration in embryo culture medium is linked to human embryo quality and viability. J Assist Reprod Genet 2022; 39:117-125. [PMID: 34845575 PMCID: PMC8866627 DOI: 10.1007/s10815-021-02368-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 11/24/2021] [Indexed: 01/03/2023] Open
Abstract
PURPOSE We aimed to evaluate the link between the GDF9 concentration in day 3 human embryo culture medium and embryo quality and viability. METHODS Two independent, prospective, observational studies were conducted. In study 1, a total of 280 embryos from 70 patients who obtained at least 4 embryos with 6-10 blastomeres (2 transferable and 2 non-transferable embryos) at day 3 were enrolled. In study 2, a total of 119 embryos from 61 patients (29 fully implanted and 32 non-implanted patients) were enrolled. The corresponding GDF9 concentrations in spent culture medium of embryos were quantified by ELISA assay. The expression pattern of GDF9 in human embryos was investigated using Q-PCR and immunofluorescence. RESULTS GDF9 mRNA and protein were detected from human oocytes to eight-cell embryos and displayed a slow decreasing trend. In study 1, GDF9 concentration in culture medium is lower for transferable embryos compared with non-transferable embryos (331 pg/mL (quartiles: 442, 664 pg/mL) vs. 518 pg/mL (quartiles: 328, 1086 pg/mL), P < 0.001), and increased commensurate with the diminution of the embryo quality (P < 0.001). In study 2, significantly lower GDF9 concentration was detected for implanted embryos than non-implanted embryos (331 pg/mL (quartiles: 156, 665 pg/mL) vs. 518 pg/mL (quartiles: 328, 1086 pg/mL), P < 0.001). The same trend was found between the embryos that led to live birth and those that failed. CONCLUSION The GDF9 concentration in culture medium is linked to embryo quality and viability, and exhibited the potential to be a non-invasive biomarker for embryo selection.
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Affiliation(s)
- Jingyu Li
- Chongqing Reproduction and Genetics Institute, Chongqing Health Center for Women and Children, No.64 Jin Tang Street, Yu Zhong District, Chongqing, 400013 China ,Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China
| | - Chong Li
- Chongqing Reproduction and Genetics Institute, Chongqing Health Center for Women and Children, No.64 Jin Tang Street, Yu Zhong District, Chongqing, 400013 China ,Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China
| | - Xuemei Liu
- Chongqing Reproduction and Genetics Institute, Chongqing Health Center for Women and Children, No.64 Jin Tang Street, Yu Zhong District, Chongqing, 400013 China ,Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China
| | - Jingwei Yang
- Chongqing Reproduction and Genetics Institute, Chongqing Health Center for Women and Children, No.64 Jin Tang Street, Yu Zhong District, Chongqing, 400013 China ,Chongqing Clinical Research Center for Reproductive Medicine, Chongqing, China
| | - Qi Zhang
- Chongqing Reproduction and Genetics Institute, Chongqing Health Center for Women and Children, No.64 Jin Tang Street, Yu Zhong District, Chongqing, 400013 China ,Chongqing Clinical Research Center for Reproductive Medicine, Chongqing, China
| | - Wei Han
- Chongqing Reproduction and Genetics Institute, Chongqing Health Center for Women and Children, No.64 Jin Tang Street, Yu Zhong District, Chongqing, 400013 China ,Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China
| | - Guoning Huang
- Chongqing Reproduction and Genetics Institute, Chongqing Health Center for Women and Children, No.64 Jin Tang Street, Yu Zhong District, Chongqing, 400013 China ,Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China ,Chongqing Clinical Research Center for Reproductive Medicine, Chongqing, China
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17
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Fernandes DP, Rossetto R, Montenegro AR, Fernandes CCL, Bravo PA, Moreno ME, Cavalcanti CM, Kubota GA, Rondina D. Effectiveness of near-infrared spectroscopy as a non-invasive tool to discriminate spectral profiles of in vitro cultured oocytes from goats. Anim Reprod 2021; 18:e20200255. [PMID: 34925556 PMCID: PMC8677351 DOI: 10.1590/1984-3143-ar2020-0255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 10/29/2021] [Indexed: 11/24/2022] Open
Abstract
Here, we aimed to discriminate between the spectral profiles of spent culture media after oocyte in vitro maturation (IVM) and culture (IVC) from goats of different ages subjected to repeated hormonal treatments. The profiles were discriminated using near infrared (NIR) spectroscopy combined with multivariate methods. A total of 19 goats (young = 10; old = 9) were subjected to serial hormonal stimulation (HS) with gonadotropins. Cumulus oophorus complexes (COCs) were collected using laparoscopic ovum pick-up (LOPU) and subjected to IVM and parthenogenetic activation. The initial embryos were subjected to IVC. Spent culture media were collected after oocyte IVM and on day 2 of IVC and analyzed using NIR spectroscopy. NIR spectral data were interpreted through chemometric methods, such as principle component analysis (PCA) and partial least square discriminant analysis (PLS-DA). The results of PCA analysis clearly showed a separation in the spectral profiles between the experimental groups (HS sessions; young and old animals) both after IVM and IVC. Overall, the main absorption bands were attributed to the C-H group second overtone, first overtone of O-H and N-H, and C-H combinations and may serve as molecular markers. On the other hand, the spectral data obtained using PLS-DA models provided a better classification of the groups. The results showed the possibility of discriminating young and old groups as well as the three HS sessions with high specificity, sensitivity, and accuracy using NIR spectra. Thus, the culture medium analysis using NIR spectroscopy combined with multivariate methods indicated the dissimilarities between the groups and provided an insight into the in vitro development of goat oocytes. This technique serves as an efficient, objective, rapid, and non-invasive method to discriminate spectral profiles.
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Affiliation(s)
- Denilsa Pires Fernandes
- Laboratório de Nutrição e Produção de Ruminantes, Faculdade de Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brasil
| | - Rafael Rossetto
- Laboratório de Nutrição e Produção de Ruminantes, Faculdade de Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brasil
| | - Assis Rubens Montenegro
- Laboratório de Nutrição e Produção de Ruminantes, Faculdade de Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brasil
| | | | - Pamela Angela Bravo
- Laboratório de Nutrição e Produção de Ruminantes, Faculdade de Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brasil
| | - Maria Eugenia Moreno
- Laboratório de Nutrição e Produção de Ruminantes, Faculdade de Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brasil
| | - Camila Muniz Cavalcanti
- Laboratório de Nutrição e Produção de Ruminantes, Faculdade de Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brasil
| | - Guilherme Araújo Kubota
- Laboratório de Nutrição e Produção de Ruminantes, Faculdade de Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brasil
| | - Davide Rondina
- Laboratório de Nutrição e Produção de Ruminantes, Faculdade de Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brasil
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18
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Khoramipour K, Sandbakk Ø, Keshteli AH, Gaeini AA, Wishart DS, Chamari K. Metabolomics in Exercise and Sports: A Systematic Review. Sports Med 2021; 52:547-583. [PMID: 34716906 DOI: 10.1007/s40279-021-01582-y] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND Metabolomics is a field of omics science that involves the comprehensive measurement of small metabolites in biological samples. It is increasingly being used to study exercise physiology and exercise-associated metabolism. However, the field of exercise metabolomics has not been extensively reviewed or assessed. OBJECTIVE This review on exercise metabolomics has three aims: (1) to provide an introduction to the general workflow and the different metabolomics technologies used to conduct exercise metabolomics studies; (2) to provide a systematic overview of published exercise metabolomics studies and their findings; and (3) to discuss future perspectives in the field of exercise metabolomics. METHODS We searched electronic databases including Google Scholar, Science Direct, PubMed, Scopus, Web of Science, and the SpringerLink academic journal database between January 1st 2000 and September 30th 2020. RESULTS Based on our detailed analysis of the field, exercise metabolomics studies fall into five major categories: (1) exercise nutrition metabolism; (2) exercise metabolism; (3) sport metabolism; (4) clinical exercise metabolism; and (5) metabolome comparisons. Exercise metabolism is the most popular category. The most common biological samples used in exercise metabolomics studies are blood and urine. Only a small minority of exercise metabolomics studies employ targeted or quantitative techniques, while most studies used untargeted metabolomics techniques. In addition, mass spectrometry was the most commonly used platform in exercise metabolomics studies, identified in approximately 54% of all published studies. Our data indicate that biomarkers or biomarker panels were identified in 34% of published exercise metabolomics studies. CONCLUSION Overall, there is an increasing trend towards better designed, more clinical, mass spectrometry-based metabolomics studies involving larger numbers of participants/patients and larger numbers of metabolites being identified.
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Affiliation(s)
- Kayvan Khoramipour
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. .,Department of Physiology and Pharmacology, Medical Faculty, Kerman University of Medical Sciences, Blvd. 22 Bahman, Kerman, Iran.
| | - Øyvind Sandbakk
- Department of Neuromedicine and Movement Science, Centre for Elite Sports Research, Norwegian University of Science and Technology, Trondheim, Norway
| | | | - Abbas Ali Gaeini
- Department of Exercise Physiology, University of Tehran, Tehran, Iran
| | - David S Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada.,Department of Computing Science, University of Alberta, AB, T6G 2E9, Edmonton, Canada
| | - Karim Chamari
- ASPETAR, Qatar Orthopaedic and Sports Medicine Hospital, Doha, Qatar
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19
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Figoli CB, Garcea M, Bisioli C, Tafintseva V, Shapaval V, Gómez Peña M, Gibbons L, Althabe F, Yantorno OM, Horton M, Schmitt J, Lasch P, Kohler A, Bosch A. A robust metabolomics approach for the evaluation of human embryos from in vitro fertilization. Analyst 2021; 146:6156-6169. [PMID: 34515271 DOI: 10.1039/d1an01191j] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The identification of the most competent embryos for transfer to the uterus constitutes the main challenge of in vitro fertilization (IVF). We established a metabolomic-based approach by applying Fourier transform infrared (FTIR) spectroscopy on 130 samples of 3-day embryo culture supernatants from 26 embryos that implanted and 104 embryos that failed. On examining the internal structure of the data by unsupervised multivariate analysis, we found that the supernatant spectra of nonimplanted embryos constituted a highly heterogeneous group. Whereas ∼40% of these supernatants were spectroscopically indistinguishable from those of successfully implanted embryos, ∼60% exhibited diverse, heterogeneous metabolic fingerprints. This observation proved to be the direct result of pregnancy's multifactorial nature, involving both intrinsic embryonic traits and external characteristics. Our data analysis strategy thus involved one-class modelling techniques employing soft independent modelling of class analogy that identified deviant fingerprints as unsuitable for implantation. From these findings, we could develop a noninvasive Fourier-transform-infrared-spectroscopy-based approach that represents a shift in the fundamental paradigm for data modelling applied in assisted-fertilization technologies.
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Affiliation(s)
- Cecilia Beatriz Figoli
- Laboratorio de Bioespectrosocpia, CINDEFI-CONICET, CCT La Plata, Facultad de Ciencias Exactas, UNLP, 1900 La Plata, Argentina.
| | - Marcelo Garcea
- PREGNA Medicina Reproductiva, C1425 AYV Ciudad Autónoma de Buenos Aires, Argentina
| | - Claudio Bisioli
- PREGNA Medicina Reproductiva, C1425 AYV Ciudad Autónoma de Buenos Aires, Argentina
| | - Valeria Tafintseva
- Faculty of Science and Technology, Norwegian University of Life Sciences, 1432 Ås, Norway.
| | - Volha Shapaval
- Faculty of Science and Technology, Norwegian University of Life Sciences, 1432 Ås, Norway.
| | - Mariana Gómez Peña
- PREGNA Medicina Reproductiva, C1425 AYV Ciudad Autónoma de Buenos Aires, Argentina
| | - Luz Gibbons
- IECS, Instituto de Efectividad Clínica y Sanitaria, C1414 Ciudad Autónoma de Buenos Aires, Argentina
| | - Fernando Althabe
- IECS, Instituto de Efectividad Clínica y Sanitaria, C1414 Ciudad Autónoma de Buenos Aires, Argentina
| | - Osvaldo Miguel Yantorno
- Laboratorio de Bioespectrosocpia, CINDEFI-CONICET, CCT La Plata, Facultad de Ciencias Exactas, UNLP, 1900 La Plata, Argentina.
| | - Marcos Horton
- PREGNA Medicina Reproductiva, C1425 AYV Ciudad Autónoma de Buenos Aires, Argentina
| | | | - Peter Lasch
- Centre for Biological Threats and Special Pathogens (ZBS) Proteomics and Spectroscopy Unit, Robert Koch-Institut, 13353 Berlin, Germany
| | - Achim Kohler
- Faculty of Science and Technology, Norwegian University of Life Sciences, 1432 Ås, Norway.
| | - Alejandra Bosch
- Laboratorio de Bioespectrosocpia, CINDEFI-CONICET, CCT La Plata, Facultad de Ciencias Exactas, UNLP, 1900 La Plata, Argentina.
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20
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Wang J, Zheng W, Zhang S, Yan K, Jin M, Hu H, Ma Z, Gong F, Lu G, Ren Y, Lin L, Lin G, Hu L, Liu S. An increase of phosphatidylcholines in follicular fluid implies attenuation of embryo quality on day 3 post-fertilization. BMC Biol 2021; 19:200. [PMID: 34503495 PMCID: PMC8428131 DOI: 10.1186/s12915-021-01118-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 08/03/2021] [Indexed: 01/02/2023] Open
Abstract
Background Although oocyte quality is the dominant factor determining embryo quality, few studies have been conducted to evaluate embryo quality based on the metabolites related to the oocyte. With quantification of the follicular fluid (FF) metabolites, in assisted reproductive technology (ART), this study sought to evaluate the embryo or oocyte quality through an informative approach. Results An evaluation model consisting of 17 features was generated to distinguish the embryo quality on day 3 post-fertilization, and phosphatidylcholines (PCs) were the key contributors to the evaluation. The model was extended to the patients under different ages and hyperstimulations, and the features were further enriched to facilitate the evaluation of the embryo quality. The metabolites were clustered through pathway analysis, leading to a hypothesis that accumulation of arachidonic acid induced by PCs might weaken embryo quality on day 3 post-fertilization. Conclusions A discriminating model with metabolic features elicited from follicular fluid was established, which enabled the evaluation of the embryo or oocyte quality even under certain clinical conditions, and the increase of PCs in follicular fluid implies the attenuation of embryo quality on day 3 post-fertilization. Supplementary Information The online version contains supplementary material available at 10.1186/s12915-021-01118-w.
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Affiliation(s)
- Ju Wang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.,BGI-Shenzhen, Shenzhen, 518083, China
| | - Wei Zheng
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008, China
| | - Shuoping Zhang
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008, China
| | - Keqiang Yan
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.,BGI-Shenzhen, Shenzhen, 518083, China
| | - Miao Jin
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008, China
| | - Huiling Hu
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Key Laboratory of National Health and Family Planning Commission, Central South University, Changsha, 410008, Hunan, China
| | - Zhen Ma
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.,BGI-Shenzhen, Shenzhen, 518083, China
| | - Fei Gong
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008, China.,Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Key Laboratory of National Health and Family Planning Commission, Central South University, Changsha, 410008, Hunan, China
| | - Guangxiu Lu
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008, China.,Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Key Laboratory of National Health and Family Planning Commission, Central South University, Changsha, 410008, Hunan, China
| | - Yan Ren
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.,BGI-Shenzhen, Shenzhen, 518083, China
| | - Liang Lin
- BGI-Shenzhen, Shenzhen, 518083, China
| | - Ge Lin
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008, China.,Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Key Laboratory of National Health and Family Planning Commission, Central South University, Changsha, 410008, Hunan, China
| | - Liang Hu
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008, China. .,Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Key Laboratory of National Health and Family Planning Commission, Central South University, Changsha, 410008, Hunan, China.
| | - Siqi Liu
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. .,BGI-Shenzhen, Shenzhen, 518083, China.
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21
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Alias AB, Huang HY, Yao DJ. A Review on Microfluidics: An Aid to Assisted Reproductive Technology. Molecules 2021; 26:4354. [PMID: 34299629 PMCID: PMC8303723 DOI: 10.3390/molecules26144354] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/14/2021] [Accepted: 07/15/2021] [Indexed: 12/20/2022] Open
Abstract
Infertility is a state of the male or female reproductive system that is defined as the failure to achieve pregnancy even after 12 or more months of regular unprotected sexual intercourse. Assisted reproductive technology (ART) plays a crucial role in addressing infertility. Various ART are now available for infertile couples. Fertilization in vitro (IVF), intracytoplasmic sperm injection (ICSI) and intrauterine insemination (IUI) are the most common techniques in this regard. Various microfluidic technologies can incorporate various ART procedures such as embryo and gamete (sperm and oocyte) analysis, sorting, manipulation, culture and monitoring. Hence, this review intends to summarize the current knowledge about the application of this approach towards cell biology to enhance ART.
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Affiliation(s)
- Anand Baby Alias
- Institute of NanoEngineering and MicroSystems, National Tsing Hua University, Hsinchu 30013, Taiwan;
| | - Hong-Yuan Huang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
- Department of Obstetrics and Gynecology, Chang Gung University and College of Medicine, Taoyuan 33305, Taiwan
| | - Da-Jeng Yao
- Institute of NanoEngineering and MicroSystems, National Tsing Hua University, Hsinchu 30013, Taiwan;
- Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan
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22
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Alipour H, Duus RK, Wimmer R, Dardmeh F, Du Plessis SS, Jørgensen N, Christiansen OB, Hnida C, Nielsen HI, Van Der Horst G. Seminal plasma metabolomics profiles following long (4-7 days) and short (2 h) sexual abstinence periods. Eur J Obstet Gynecol Reprod Biol 2021; 264:178-183. [PMID: 34325212 DOI: 10.1016/j.ejogrb.2021.07.024] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/08/2021] [Accepted: 07/12/2021] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Metabolomic profiling of seminal plasma has been suggested as a possible approach for a fast and non-invasive male infertility evaluation diagnosis. However, metabolomics profiles in normozoospermic men have not been thoroughly investigated, and the influence of ejaculation-abstinence has not been described. To provide interim reference values and find associations between the metabolomics profiles of human seminal plasma and length of ejaculation-abstinence period in normozoospermic men. STUDY DESIGN Semen samples collected after long (4-7 days) and short abstinence (2 h) from 31 normozoospermic males were assessed for routine quality parameters before the seminal plasma was separated by centrifugation. Metabolomics profiles of the seminal plasma were then determined using untargeted Nuclear Magnetic Resonance Spectroscopy. RESULTS In total, 30 metabolites were identified. Pyruvate showed a higher concentration, while fructose, acetate, choline, methanol, N-acetylglucosamine, O-acetylcarnitine, uridine, and sn-glycero-3-phosphocoline showed lower concentrations in samples collected after short abstinence (vs. long). All metabolites showed lower absolute amounts (volume × concentration) following shorter abstinence. However, the lower sperm concentration in samples collected after short abstinence resulted in higher absolute amounts of pyruvate and taurine per spermatozoa: pyruvate 1.92 (1.12-3.87) vs. 1.29 (0.83-2.62) (P < 0.001) and taurine 0.58 (0.36-0.92) vs. 0.43 (0.28-0.95) (P < 0.05) ng/106 spermatozoa. Simultaneously, there was a higher percentage of progressively motile spermatozoa in samples collected after the short abstinence. CONCLUSION The generally lower concentrations of seminal metabolites after short abstinence periods may be related to the shorter time available for secretion and collection of these metabolites by the accessory glands and the epididymides. The concomitant lower number of spermatozoa in the second ejaculate resulted in increased absolute amounts of pyruvate and taurine per spermatozoa, accompanied by increased spermatozoa motility in these samples. The simultaneous increase in percentages of motile spermatozoa and absolute amounts of pyruvate and taurine per spermatozoa after shorter abstinence might indicate that these two metabolites play a more critical role in sperm motility, which should be further investigated in future studies.
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Affiliation(s)
- H Alipour
- Department of Health Science and Technology, Regenerative Medicine Group, Aalborg University, Aalborg, Denmark.
| | - R K Duus
- Department of Health Science and Technology, Regenerative Medicine Group, Aalborg University, Aalborg, Denmark
| | - R Wimmer
- Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark
| | - F Dardmeh
- Department of Health Science and Technology, Regenerative Medicine Group, Aalborg University, Aalborg, Denmark
| | - S S Du Plessis
- Department of Basic Medical Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates; Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
| | - N Jørgensen
- University Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen, Denmark
| | - O B Christiansen
- Department of Obstetrics and Gynecology, Fertility Unit, Aalborg University Hospital, Aalborg, Denmark; Institute of Clinical Medicine, Aalborg University, Denmark
| | - C Hnida
- Department of Obstetrics and Gynecology, Fertility Unit, Aalborg University Hospital, Aalborg, Denmark
| | - H I Nielsen
- Department of Health Science and Technology, Regenerative Medicine Group, Aalborg University, Aalborg, Denmark
| | - G Van Der Horst
- Department of Medical Biosciences, University of the Western Cape, Cape Town, South Africa
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23
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Chumachenko MS, Waseem TV, Fedorovich SV. Metabolomics and metabolites in ischemic stroke. Rev Neurosci 2021; 33:181-205. [PMID: 34213842 DOI: 10.1515/revneuro-2021-0048] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 06/09/2021] [Indexed: 12/27/2022]
Abstract
Stroke is a major reason for disability and the second highest cause of death in the world. When a patient is admitted to a hospital, it is necessary to identify the type of stroke, and the likelihood for development of a recurrent stroke, vascular dementia, and depression. These factors could be determined using different biomarkers. Metabolomics is a very promising strategy for identification of biomarkers. The advantage of metabolomics, in contrast to other analytical techniques, resides in providing low molecular weight metabolite profiles, rather than individual molecule profiles. Technically, this approach is based on mass spectrometry and nuclear magnetic resonance. Furthermore, variations in metabolite concentrations during brain ischemia could alter the principal neuronal functions. Different markers associated with ischemic stroke in the brain have been identified including those contributing to risk, acute onset, and severity of this pathology. In the brain, experimental studies using the ischemia/reperfusion model (IRI) have shown an impaired energy and amino acid metabolism and confirmed their principal roles. Literature data provide a good basis for identifying markers of ischemic stroke and hemorrhagic stroke and understanding metabolic mechanisms of these diseases. This opens an avenue for the successful use of identified markers along with metabolomics technologies to develop fast and reliable diagnostic tools for ischemic and hemorrhagic stroke.
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Affiliation(s)
- Maria S Chumachenko
- Department of Biochemistry, Faculty of Biology, Belarusian State University, Kurchatova St., 10, Minsk220030, Belarus
| | | | - Sergei V Fedorovich
- Department of Biochemistry, Faculty of Biology, Belarusian State University, Kurchatova St., 10, Minsk220030, Belarus
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24
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Chen P, Huang C, Sun Q, Zhong H, Xiong F, Liu S, Yao Z, Liu Z, Wan C, Zeng Y, Diao L. Granulocyte-Macrophage Colony Stimulating Factor in Single Blastocyst Conditioned Medium as a Biomarker for Predicting Implantation Outcome of Embryo. Front Immunol 2021; 12:679839. [PMID: 34276668 PMCID: PMC8278135 DOI: 10.3389/fimmu.2021.679839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 06/14/2021] [Indexed: 11/13/2022] Open
Abstract
Background It is highly desirable to develop new strategies based on secretomics to more accurately selection of embryos with the highest developmental potential for transfer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to promote embryo development and pregnancy establishment. However, the predictive value of GM-CSF in single blastocyst selection remains unclear. This study is to determine the concentration of GM-CSF in human single-blastocyst conditioned medium (SBCM) and to evaluate its association with embryo quality and pregnancy outcome. Methods The patients with ≤38 years of age receiving the first cycle of assisted reproductive therapy were included in this study. The patients who had <4 top-quality embryos formed by the fertilized two pronuclear zygotes on day 3 were excluded. A total of 126 SBCM samples (SBCMs) were included, of which blastocysts from 77 SBCMs were later transferred in subsequent frozen-thawed embryo transfer. The concentrations of GM-CSF were detected by single-molecule array (SIMOA) and analyzed for their possible association with embryo quality and pregnancy outcomes. The top-quality embryo (TQ), positive HCG (HP), clinical pregnancy (CP), and ongoing pregnancy (OP) rates were determined and compared between groups divided based on GM-CSF concentrations. Results The detection rate of GM-CSF was found to be 50% in all SBCMs. There were significant differences in TQ rate, HP rate, CP rate and OP rate among high concentration group, medium concentration group and low concentration group. Both GM-CSF alone or GM-CSF combined with the morphological score (MS) had a greater AUC of ROC curve than that of MS alone to predict the pregnancy outcome, and GM-CSF combined with MS had the highest AUC. Conclusions The concentration of GM-CSF in SBCM was detected at fg/ml levels, which was associated with embryo quality and pregnancy outcome. Collectively, GM-CSF may be used as a biomarker for prediction of pregnancy outcome and selection of embryos with high developmental potential for transfer in assisted reproductive technology (ART).
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Affiliation(s)
- Peilin Chen
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Chunyu Huang
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.,Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Qing Sun
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Huixian Zhong
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Feng Xiong
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Su Liu
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Zhihong Yao
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Zhiqiang Liu
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Caiyun Wan
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Yong Zeng
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Lianghui Diao
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
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25
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Gongadashetti K, Gupta P, Dada R, Malhotra N. Follicular fluid oxidative stress biomarkers and ART outcomes in PCOS women undergoing in vitro fertilization: A cross-sectional study. Int J Reprod Biomed 2021; 19:449-456. [PMID: 34278198 PMCID: PMC8261096 DOI: 10.18502/ijrm.v19i5.9254] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 08/26/2020] [Accepted: 10/20/2020] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Polycystic ovarian syndrome (PCOS) is the most common cause of anovulatory infertility. Oxidative stress (OS), which plays an important role in determining the developmental competence of an oocyte, may be involved in understanding infertility and poor outcomes cycles in PCOS women undergoing in vitro fertilization (IVF). OBJECTIVE To measure OS biomarkers in the follicular fluid of PCOS women undergoing IVF. MATERIALS AND METHODS In this cross-sectional study, 100 women with PCOS (n = 43) and tubal factor (n = 57) undergoing IVF, who were referred to a tertiary medical center between January 2016 and September 2017 were enrolled. OS markers like reactive oxygen species (ROS), total antioxidant capacity (TAC), and 8-Isoprostane (8-IP) were tested in the follicular fluid and various IVF outcomes in the form of oocytes retrieved, fertilized, cleavage rate, grading of embryos and pregnancy outcomes were compared between the two groups. RESULTS The results indicated that the levels of ROS, TAC, and 8-IP were higher in the PCOS group compared to the tubal group (p = 0.21, p = 0.95, and p < 0.05, respectively). Biomarkers based on the number of retrieved oocytes, cleavage rate, and grades of embryos did not differ significantly in the two groups. The median ROS, TAC, and 8-IP were not significantly different in the two groups in relation to the pregnancies, although the 8-IP levels were significantly raised in the PCOS women who had a miscarriage (p = 0.02). CONCLUSION This study concluded the possible role of OS in PCOS women with increased higher level of 8-IP biomarker as a potential biomarker that needs further evaluation.
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Affiliation(s)
- Kaivalya Gongadashetti
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Pankush Gupta
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Rima Dada
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
| | - Neena Malhotra
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
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26
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Siristatidis C, Stavros S, Drakeley A, Bettocchi S, Pouliakis A, Drakakis P, Papapanou M, Vlahos N. Omics and Artificial Intelligence to Improve In Vitro Fertilization (IVF) Success: A Proposed Protocol. Diagnostics (Basel) 2021; 11:diagnostics11050743. [PMID: 33919350 PMCID: PMC8143333 DOI: 10.3390/diagnostics11050743] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 04/17/2021] [Accepted: 04/19/2021] [Indexed: 02/06/2023] Open
Abstract
The prediction of in vitro fertilization (IVF) outcome is an imperative achievement in assisted reproduction, substantially aiding infertile couples, health systems and communities. To date, the assessment of infertile couples depends on medical/reproductive history, biochemical indications and investigations of the reproductive tract, along with data obtained from previous IVF cycles, if any. Our project aims to develop a novel tool, integrating omics and artificial intelligence, to propose optimal treatment options and enhance treatment success rates. For this purpose, we will proceed with the following: (1) recording subfertile couples’ lifestyle and demographic parameters and previous IVF cycle characteristics; (2) measurement and evaluation of metabolomics, transcriptomics and biomarkers, and deep machine learning assessment of the oocyte, sperm and embryo; (3) creation of artificial neural network models to increase objectivity and accuracy in comparison to traditional techniques for the improvement of the success rates of IVF cycles following an IVF failure. Therefore, “omics” data are a valuable parameter for embryo selection optimization and promoting personalized IVF treatment. “Omics” combined with predictive models will substantially promote health management individualization; contribute to the successful treatment of infertile couples, particularly those with unexplained infertility or repeated implantation failures; and reduce multiple gestation rates.
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Affiliation(s)
- Charalampos Siristatidis
- Second Department of Obstetrics and Gynecology, “Aretaieion Hospital”, Medical School, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528 Athens, Greece; (M.P.); (N.V.)
- Assisted Reproduction Unit, Second Department of Obstetrics and Gynecology, “Aretaieion Hospital”, Medical School, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528 Athens, Greece
- Correspondence: ; Tel.: +30-69-3229-4994
| | - Sofoklis Stavros
- Assisted Reproduction Unit, First Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Alexandra Hospital, 80 Vas. Sofias Av. and Lourou str., 11528 Athens, Greece; (S.S.); (P.D.)
| | - Andrew Drakeley
- Hewitt Fertility Centre, Liverpool Women’s NHS Foundation Trust, Crown Street, Liverpool L8 7SS, UK;
| | - Stefano Bettocchi
- Second Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncologic Science, Policlinico University of Bari, 70124 Bari, Italy;
| | - Abraham Pouliakis
- Second Department of Pathology, National and Kapodistrian University of Athens, “Attikon” University Hospital, Rimini 1, Chaidari, 12642 Athens, Greece;
| | - Peter Drakakis
- Assisted Reproduction Unit, First Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Alexandra Hospital, 80 Vas. Sofias Av. and Lourou str., 11528 Athens, Greece; (S.S.); (P.D.)
| | - Michail Papapanou
- Second Department of Obstetrics and Gynecology, “Aretaieion Hospital”, Medical School, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528 Athens, Greece; (M.P.); (N.V.)
| | - Nikolaos Vlahos
- Second Department of Obstetrics and Gynecology, “Aretaieion Hospital”, Medical School, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528 Athens, Greece; (M.P.); (N.V.)
- Assisted Reproduction Unit, Second Department of Obstetrics and Gynecology, “Aretaieion Hospital”, Medical School, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528 Athens, Greece
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27
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Pourasil RSM, Gilany K. Fast diagnosis of men's fertility using Raman spectroscopy combined with chemometric methods: An experimental study. Int J Reprod Biomed 2021; 19:121-128. [PMID: 33718756 PMCID: PMC7922295 DOI: 10.18502/ijrm.v19i2.8470] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Revised: 12/04/2019] [Accepted: 07/07/2020] [Indexed: 11/24/2022] Open
Abstract
Background Idiopathic infertile men suffer from unexplained male infertility; they are infertile despite having a normal semen analysis, a normal history, and physical examination, and when female infertility factor has been ruled out. Objective The present study aimed to develop a metabolic fingerprinting methodology using Raman spectroscopy combined with Chemometrics to detect idiopathic infertile men vs. fertile ones by seminal plasma. Materials and Methods In this experimental study, the seminal plasma of 26 men including 13 fertile and 13 with unexplained infertility who reffered to, Avicenna Infertility Clinic, 2018, Tehran, Iran, have been investigated. The seminal metabolomic fingerprinting was evaluated using Raman spectrometer from 100 to 4250 cm-1. The principal component analysis and discriminate analysis methods were used. Results The total of 26 samples were divided into 20 training and 6 test sets. The Principal component analysis score plot of the training set showed that the data were perfectly divided into two sides of the plot, which statistically approves the direct effect of semen metabolome changes on the Raman spectra. A classification model was constructed by linear discriminant analysis using the training set and evaluated by the test group which resulted in completely correct classification. While three of the six test samples appeared in the fertile group, the rest appeared in the infertile as expected. Conclusion Metabolic fingerprinting of seminal plasma using Raman spectroscopy combined with chemometric classification methods accurately discriminated between the idiopathic infertile men and the fertile ones and predicted their fertility type.
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Affiliation(s)
| | - Kambiz Gilany
- Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECER, Tehran, Iran.,Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
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28
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Coticchio G, Behr B, Campbell A, Meseguer M, Morbeck DE, Pisaturo V, Plancha CE, Sakkas D, Xu Y, D'Hooghe T, Cottell E, Lundin K. Fertility technologies and how to optimize laboratory performance to support the shortening of time to birth of a healthy singleton: a Delphi consensus. J Assist Reprod Genet 2021; 38:1021-1043. [PMID: 33599923 DOI: 10.1007/s10815-021-02077-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 01/18/2021] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To explore how the assisted reproductive technology (ART) laboratories can be optimized and standardized to enhance embryo culture and selection, to bridge the gap between standard practice and the new concept of shortening time to healthy singleton birth. METHODS A Delphi consensus was conducted (January to July 2018) to assess how the ART laboratory could be optimized, in conjunction with existing guidelines, to reduce the time to a healthy singleton birth. Eight experts plus the coordinator discussed and refined statements proposed by the coordinator. The statements were distributed via an online survey to 29 participants (including the eight experts from step 1), who voted on their agreement/disagreement with each statement. Consensus was reached if ≥ 66% of participants agreed/disagreed with a statement. If consensus was not achieved for any statement, that statement was revised and the process repeated until consensus was achieved. Details of statements achieving consensus were communicated to the participants. RESULTS Consensus was achieved for all 13 statements, which underlined the need for professional guidelines and standardization of lab processes to increase laboratory competency and quality. The most important points identified were the improvement of embryo culture and embryo assessment to shorten time to live birth through the availability of more high-quality embryos, priority selection of the most viable embryos and improved cryosurvival. CONCLUSION The efficiency of the ART laboratory can be improved through professional guidelines on standardized practices and optimized embryo culture environment, assessment, selection and cryopreservation methodologies, thereby reducing the time to a healthy singleton delivery.
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Affiliation(s)
- Giovanni Coticchio
- 9.baby Family and Fertility Center, Via Dante, 15, 40125, Bologna, Italy.
| | - Barry Behr
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, Stanford University School of Medicine, Stanford, CA, USA
| | | | | | - Dean E Morbeck
- Fertility Associates, Auckland, New Zealand
- Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Valerio Pisaturo
- Reproductive Medicine Department, International Evangelical Hospital, Genoa, Italy
| | - Carlos E Plancha
- Inst. Histologia e Biologia do Desenvolvimento, Faculdade de Medicina, Universidade de Lisboa and CEMEARE, Lisbon, Portugal
| | - Denny Sakkas
- Boston IVF, Waltham, MA, USA
- Department of Obstetrics and Gynecology, Yale University, New Haven, CT, USA
| | - Yanwen Xu
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Thomas D'Hooghe
- Department of Obstetrics and Gynecology, Yale University, New Haven, CT, USA
- Global Medical Affairs Fertility, R&D Biopharma, Merck KGaA, Darmstadt, Germany
- Department of Development and Regeneration, Biomedical Sciences Group, KU Leuven (University of Leuven), Leuven, Belgium
| | - Evelyn Cottell
- Global Medical Affairs Fertility, R&D Biopharma, Merck KGaA, Darmstadt, Germany
| | - Kersti Lundin
- Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
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29
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Feofanova EV, Chen H, Dai Y, Jia P, Grove ML, Morrison AC, Qi Q, Daviglus M, Cai J, North KE, Laurie CC, Kaplan RC, Boerwinkle E, Yu B. A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos. Am J Hum Genet 2020; 107:849-863. [PMID: 33031748 PMCID: PMC7675000 DOI: 10.1016/j.ajhg.2020.09.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 09/10/2020] [Indexed: 02/08/2023] Open
Abstract
Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%-54% with a median at 2.5%. We discovered 46 variant-metabolite pairs (p value < 1.2 × 10-10, minor allele frequency ≥ 1%, proportion of variance explained [PEV] mean = 3.4%, PEVrange = 1%-22%) with generalized effects in two population-based studies and confirmed 301 known locus-metabolite associations. Half of the identified variants with generalized effect were located in genes, including five nonsynonymous variants. We identified co-localization with the expression quantitative trait loci at 105 discovered and 151 known loci-metabolites sets. rs5855544, upstream of SLC51A, was associated with higher levels of three steroid sulfates and co-localized with expression levels of SLC51A in several tissues. Mendelian randomization (MR) analysis identified several metabolites associated with coronary heart disease (CHD) and type 2 diabetes. For example, two variants located in or near CYP4F2 (rs2108622 and rs79400241, respectively), involved in vitamin E metabolism, were associated with the levels of octadecanedioate and vitamin E metabolites (gamma-CEHC and gamma-CEHC glucuronide); MR analysis showed that genetically high levels of these metabolites were associated with lower odds of CHD. Our findings document the genetic architecture of circulating metabolites in an underrepresented Hispanic/Latino community, shedding light on disease etiology.
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Affiliation(s)
- Elena V Feofanova
- Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA
| | - Han Chen
- Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA; Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Yulin Dai
- Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Peilin Jia
- Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Megan L Grove
- Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA
| | - Alanna C Morrison
- Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA
| | - Qibin Qi
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Martha Daviglus
- Institute for Minority Health Research, University of Illinois College of Medicine, Chicago, IL 60612, USA
| | - Jianwen Cai
- Department of Biostatistics, University of North Carolina Gilling School of Global Public Health, Chapel Hill, NC 27599, USA
| | - Kari E North
- Department of Epidemiology, University of North Carolina Gilling School of Global Public Health, Chapel Hill, NC 27599, USA; Carolina Center of Genome Sciences, University of North Carolina, Chapel Hill, NC 27514, USA
| | - Cathy C Laurie
- Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
| | - Robert C Kaplan
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
| | - Eric Boerwinkle
- Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA
| | - Bing Yu
- Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA.
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Asampille G, Cheredath A, Joseph D, Adiga SK, Atreya HS. The utility of nuclear magnetic resonance spectroscopy in assisted reproduction. Open Biol 2020; 10:200092. [PMID: 33142083 PMCID: PMC7729034 DOI: 10.1098/rsob.200092] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 10/13/2020] [Indexed: 12/21/2022] Open
Abstract
Infertility affects approximately 15-20% of individuals of reproductive age worldwide. Over the last 40 years, assisted reproductive technology (ART) has helped millions of childless couples. However, ART is limited by a low success rate and risk of multiple gestations. Devising methods for selecting the best gamete or embryo that increases the ART success rate and prevention of multiple gestation has become one of the key goals in ART today. Special emphasis has been placed on the development of non-invasive approaches, which do not require perturbing the embryonic cells, as the current morphology-based embryo selection approach has shortcomings in predicting the implantation potential of embryos. An observed association between embryo metabolism and viability has prompted researchers to develop metabolomics-based biomarkers. Nuclear magnetic resonance (NMR) spectroscopy provides a non-invasive approach for the metabolic profiling of tissues, gametes and embryos, with the key advantage of having a minimal sample preparation procedure. Using NMR spectroscopy, biologically important molecules can be identified and quantified in intact cells, extracts or secretomes. This, in turn, helps to map out the active metabolic pathways in a system. The present review covers the contribution of NMR spectroscopy in assisted reproduction at various stages of the process.
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Affiliation(s)
- Gitanjali Asampille
- Department of Clinical Embryology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India
| | - Aswathi Cheredath
- Department of Clinical Embryology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India
| | - David Joseph
- NMR Research Centre, Indian Institute of Science, Bangalore 560012, India
- Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India
| | - Satish K. Adiga
- Department of Clinical Embryology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India
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Fraga-Corral M, Carpena M, Garcia-Oliveira P, Pereira AG, Prieto MA, Simal-Gandara J. Analytical Metabolomics and Applications in Health, Environmental and Food Science. Crit Rev Anal Chem 2020; 52:712-734. [DOI: 10.1080/10408347.2020.1823811] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- M. Fraga-Corral
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Bragança, Portugal
| | - M. Carpena
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain
| | - P. Garcia-Oliveira
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Bragança, Portugal
| | - A. G. Pereira
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Bragança, Portugal
| | - M. A. Prieto
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain
| | - J. Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain
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32
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Hu C, Chen Y, Cao Y, Jia Y, Zhang J. Metabolomics analysis reveals the protective effect of quercetin-3-O-galactoside (Hyperoside) on liver injury in mice induced by acetaminophen. J Food Biochem 2020; 44:e13420. [PMID: 32744346 DOI: 10.1111/jfbc.13420] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 07/15/2020] [Accepted: 07/16/2020] [Indexed: 11/27/2022]
Abstract
We investigated the protective effect of Hyperoside (HPS) on liver injury induced by acetaminophen (APAP) in C57 mice. HPS was administered orally for 7 days and APAP was administered orally on the 7th day. Serum and liver samples were then collected for biochemical analyses, histopathology assessments, and metabolomics studies. Metabolites were assessed using a UHPLC-MS system. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to process the data. Pathway analyses were performed using Metaboanalyst 4.0. Western blot and qRT-PCR were used to determine the protein and mRNA levels, respectively. HPS interacted with active sites in CYP2E1 and caused protein degradation. In conclusion, our results suggested that HPS prevented the oxidative stress-induced liver injury caused by APAP. PRACTICAL APPLICATIONS: Hyperoside was shown to have potential protective and therapeutic effects against liver diseases. Male C57 mice were used to perform pharmacodynamic, pharmacology, and metabolomics evaluations. At a dose of 60 mg/kg, HPS prevented oxidative stress-induced liver injury caused by APAP by regulating the glutathione-related metabolites and enzymes through the inhibition of CYP2E1.
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Affiliation(s)
- Cheng Hu
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ying Chen
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yiyuan Cao
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yiqun Jia
- Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiaqi Zhang
- Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Stigliani S, Orlando G, Massarotti C, Casciano I, Bovis F, Anserini P, Ubaldi FM, Remorgida V, Rienzi L, Scaruffi P. Non-invasive mitochondrial DNA quantification on Day 3 predicts blastocyst development: a prospective, blinded, multi-centric study. Mol Hum Reprod 2020; 25:527-537. [PMID: 31174207 DOI: 10.1093/molehr/gaz032] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 04/19/2019] [Indexed: 12/28/2022] Open
Abstract
In ART, embryo quality evaluation is routinely based on morphological criteria. We previously demonstrated that the mitochondrial DNA (mtDNA)/genomic DNA (gDNA) ratio in culture medium was significantly associated with embryo quality and viability potential. The purpose of this prospective, blinded, multi-centric study was to validate the use of mtDNA/gDNA ratio in Day 3 spent medium as a predictor of human embryo developmental competence. The mtDNA/gDNA ratio was assessed in Day 3 culture media (n=484) of embryos from 143 patients by quantitative PCR. A mixed effect logistic regression model was applied. We found that mtDNA/gDNA ratio in Day 3 culture medium combined with embryo morphology improves the prediction upon blastulation compared to morphology alone (P < 0.0001), independent of patient and cycle characteristics. With regard to routine use in clinics, we evaluated the ability of the novel, combined grading score to improve selection of developmentally competent embryos of a single cohort. Including embryos from 44 patients, the sensibility and specificity of the scoring system based on Day 3 morphological stage were 92% and 13%, respectively. Integration with the culture medium mtDNA/gDNA ratio increased the performance of the method (sensibility: 95%; specificity: 65%). The results of this study suggest the possibility of carrying out a non-invasive evaluation of embryonic mtDNA content through the culture medium. When combined with embryo morphology, it has the potential to help embryologists rank embryos and choose which embryo(s) has the greater development potential, and thus should be transferred on Day 3, among sibling embryos with the same morphological grade.
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Affiliation(s)
- Sara Stigliani
- UOS Physiopathology of Human Reproduction, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | | | - Claudia Massarotti
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Academic Unit of Obstetrics and Gynecology, University of Genova, Genova, Italy
| | - Ida Casciano
- UOS Physiopathology of Human Reproduction, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Francesca Bovis
- Department of Health Sciences (DISSAL), University of Genova, Genova, Italy
| | - Paola Anserini
- UOS Physiopathology of Human Reproduction, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | | | - Valentino Remorgida
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Academic Unit of Obstetrics and Gynecology, University of Genova, Genova, Italy
| | - Laura Rienzi
- GENERA, Reproductive Medicine Center, Roma, Italy
| | - Paola Scaruffi
- UOS Physiopathology of Human Reproduction, IRCCS Ospedale Policlinico San Martino, Genova, Italy
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34
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Parvanov D, Nikolova D, Ganeva R, Nikolova K, Vasileva M, Rangelov I, Pancheva M, Serafimova M, Staneva R, Hadjidekova S, Scarpellini F, Stamenov G. Unbalanced human embryos secrete more hyperglycosylated human chorionic gonadotrophin (hCG-H) than balanced ones. J Assist Reprod Genet 2020; 37:1341-1348. [PMID: 32323120 PMCID: PMC7311563 DOI: 10.1007/s10815-020-01776-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 04/08/2020] [Indexed: 10/24/2022] Open
Abstract
PURPOSE The aim of this study was to compare the levels of hyperglycosylated human chorionic gonadotropin (hCG-H) secreted from balanced and unbalanced human embryos. METHODS Single-step culture media samples from 155 good quality embryos, derived from 90 good prognosis patients undergoing intracytoplasmic sperm injection (ICSI), were collected on the fifth day of embryo cultivation. All embryos were tested by next-generation sequencing (NGS) technique. The hCG-H levels in the culture media were evaluated by ELISA kit (Cusabio Biotech, CBS-E15803h) according to the manufacturer's instructions. Statistical analysis was performed using SPSS v.21 (IBM Corp., Armonk, NY, USA). RESULTS The NGS analysis revealed that 36% of the embryos (n = 56) were balanced, and 64% of the embryos were unbalanced (n = 99). The presence of hCG-H was confirmed in all embryo culture media samples but was absent in the negative control. In addition, hCG-H concentration was significantly higher in the culture media from unbalanced embryos compared with the balanced ones (0.72 ± 0.30 mIU/ml vs. 0.62 ± 0.12 mIU/ml, p = 0.02, respectively). Furthermore, the mean levels of hCG-H were significantly increased in the samples from embryos with multiple abnormalities. Finally, the highest levels of hCG-H were expressed from embryos with monosomy of chromosome 11 (1.28 ± 0.04 mIU/ml) and those with trisomies of chromosomes 21 (2.23 mIU/ml) and 4 (1.02 ± 0.35 mIU/ml). CONCLUSION Our results suggest that chromosomal aberrations in human embryos are associated with an increased secretion of hCG-H. However, hCG-H concentration in embryo culture media as a single biomarker is not sufficient for an accurate selection of balanced embryos.
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Affiliation(s)
- Dimitar Parvanov
- Nadezhda Women's Health Hospital, 3 "Blaga vest" Street, Sofia, Bulgaria.
| | - Dragomira Nikolova
- Department of Medical Genetics, Medical Faculty, Medical University - Sofia, Sofia, Bulgaria
| | - Rumiana Ganeva
- Nadezhda Women's Health Hospital, 3 "Blaga vest" Street, Sofia, Bulgaria
| | - Kristina Nikolova
- Nadezhda Women's Health Hospital, 3 "Blaga vest" Street, Sofia, Bulgaria
| | - Magdalena Vasileva
- Nadezhda Women's Health Hospital, 3 "Blaga vest" Street, Sofia, Bulgaria
| | - Ivaylo Rangelov
- Nadezhda Women's Health Hospital, 3 "Blaga vest" Street, Sofia, Bulgaria
| | - Maria Pancheva
- Nadezhda Women's Health Hospital, 3 "Blaga vest" Street, Sofia, Bulgaria
| | - Maria Serafimova
- Nadezhda Women's Health Hospital, 3 "Blaga vest" Street, Sofia, Bulgaria
| | - Rada Staneva
- Department of Medical Genetics, Medical Faculty, Medical University - Sofia, Sofia, Bulgaria
| | - Savina Hadjidekova
- Department of Medical Genetics, Medical Faculty, Medical University - Sofia, Sofia, Bulgaria
| | | | - Georgi Stamenov
- Nadezhda Women's Health Hospital, 3 "Blaga vest" Street, Sofia, Bulgaria
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35
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Chen P, Sun Q, Xiong F, Zhong H, Yao Z, Zeng Y. A method for the detection of hCG β in spent embryo culture medium based on multicolor fluorescence detection from microfluidic droplets. BIOMICROFLUIDICS 2020; 14:024107. [PMID: 32549919 PMCID: PMC7156014 DOI: 10.1063/1.5141490] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 03/05/2020] [Indexed: 05/04/2023]
Abstract
The evaluation of embryo quality via human chorionic gonadotropin beta (hCG β) and other proteins secreted by embryos in a spent embryo culture medium (SECM) receives a close review in the field of assisted reproduction. However, accurate and quantitative detection of these trace proteins is still a challenge. In this study, a highly sensitive protein detection method using microfluidic droplets and multicolor fluorescence detection was developed and used to detect hCG β secreted by embryos in SECM. β-Galactosidase (β-Gal) was used to label hCG β and can catalyze the conversion of nonfluorescent substrate fluorescein di-β-d-galactopyranoside to produce fluorescein to amplify the signal strength. Compared with previous studies, the proposed method requires only a simple microfluidic chip and can eliminate false-positive signals generated by free β-Gal through simultaneous detection of fluorescence, which can ensure the accuracy of the results. The lower detection limit of hCG β was 0.1 pg/ml. Using the developed method, hCG β in SECM was successfully detected; the hCG β secreted by top-quality blastocysts was significantly higher than that of non-top-quality blastocysts and embryos that do not develop into blastocysts. The proposed method can be used to detect secretory proteins from embryos in SECM and has application value in the screening of other biomarkers.
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Affiliation(s)
- Peilin Chen
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, Guangdong, People's Republic of China
| | - Qing Sun
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, Guangdong, People's Republic of China
| | - Feng Xiong
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, Guangdong, People's Republic of China
| | - Huixian Zhong
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, Guangdong, People's Republic of China
| | - Zhihong Yao
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, Guangdong, People's Republic of China
| | - Yong Zeng
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, Guangdong, People's Republic of China
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36
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McLennan HJ, Saini A, Dunning KR, Thompson JG. Oocyte and embryo evaluation by AI and multi-spectral auto-fluorescence imaging: Livestock embryology needs to catch-up to clinical practice. Theriogenology 2020; 150:255-262. [PMID: 32088032 DOI: 10.1016/j.theriogenology.2020.01.061] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 01/28/2020] [Indexed: 02/08/2023]
Abstract
A highly accurate 'non-invasive quantitative embryo assessment for pregnancy' (NQEAP) technique that determines embryo quality has been an elusive goal. If developed, NQEAP would transform the selection of embryos from both Multiple Ovulation and Embryo Transfer (MOET), and even more so, in vitro produced (IVP) embryos for livestock breeding. The area where this concept is already having impact is in the field of clinical embryology, where great strides have been taken in the application of morphokinetics and artificial intelligence (AI); while both are already in practice, rigorous and robust evidence of efficacy is still required. Even the translation of advances in the qualitative scoring of human IVF embryos have yet to be translated to the livestock IVP industry, which remains dependent on the MOET-standardised 3-point scoring system. Furthermore, there are new ways to interrogate the biochemistry of individual embryonic cells by using new, light-based methodologies, such as FLIM and hyperspectral microscopy. Combinations of these technologies, in particular combining new imaging systems with AI, will lead to very accurate NQEAP predictive tools, improving embryo selection and recipient pregnancy success.
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Affiliation(s)
- H J McLennan
- Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, SA, 5005, Australia; ARC Centre of Excellence for Nanoscale BioPhotonics & Institute for Photonics and Advanced Sensing, The University of Adelaide, Adelaide, SA, 5005, Australia
| | - A Saini
- Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, SA, 5005, Australia; ARC Centre of Excellence for Nanoscale BioPhotonics & Institute for Photonics and Advanced Sensing, The University of Adelaide, Adelaide, SA, 5005, Australia
| | - K R Dunning
- Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, SA, 5005, Australia; ARC Centre of Excellence for Nanoscale BioPhotonics & Institute for Photonics and Advanced Sensing, The University of Adelaide, Adelaide, SA, 5005, Australia
| | - J G Thompson
- Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, SA, 5005, Australia; ARC Centre of Excellence for Nanoscale BioPhotonics & Institute for Photonics and Advanced Sensing, The University of Adelaide, Adelaide, SA, 5005, Australia.
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Matorras R, Martinez-Arranz I, Arretxe E, Iruarrizaga-Lejarreta M, Corral B, Ibañez-Perez J, Exposito A, Prieto B, Elortza F, Alonso C. The lipidome of endometrial fluid differs between implantative and non-implantative IVF cycles. J Assist Reprod Genet 2019; 37:385-394. [PMID: 31865491 DOI: 10.1007/s10815-019-01670-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 12/13/2019] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE To characterize the most relevant changes in the lipidome of endometrial fluid aspirate (EFA) in non-implantative cycles. DESIGN Lipidomics in a prospective cohort study. SETTINGS Reproductive unit of a university hospital. PATIENTS Twenty-nine women undergoing an IVF cycle. Fifteen achieved pregnancy and 14 did not. INTERVENTION Endometrial fluid aspiration immediately before performing embryo transfer. MAIN OUTCOME MEASURES Clinical pregnancy rate and lipidomic profiles obtained on an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based analytical platform. RESULTS The comparative analysis of the lipidomic patterns of endometrial fluid in implantative and non-implantative IVF cycles revealed eight altered metabolites: seven glycerophospholipids and an omega-6 polyunsaturated fatty acid. Then, women with a non-implantative cycle were accurately classified with a support vector machine algorithm including these eight lipid metabolites. The diagnostic performances of the algorithm showed an area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of 0.893 ± 0.07, 85.7%, 80.0%, and 82.8%, respectively. CONCLUSION A predictive lipidomic signature linked to the implantative status of the endometrial fluid has been found.
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Affiliation(s)
- Roberto Matorras
- Human Reproduction Unit, Cruces University Hospital, BioCruces, University of the Basque Country, Bilbao, Spain. .,Instituto Valenciano de Infertilidad, IVI, Bilbao, Spain.
| | | | - Enara Arretxe
- OWL Metabolomics, Parque Tecnológico de Bizkaia, Derio, Spain
| | | | - Blanca Corral
- Human Reproduction Unit, Cruces University Hospital, BioCruces, University of the Basque Country, Bilbao, Spain
| | - Jone Ibañez-Perez
- Human Reproduction Unit, Cruces University Hospital, BioCruces, University of the Basque Country, Bilbao, Spain
| | - Antonia Exposito
- Human Reproduction Unit, Cruces University Hospital, BioCruces, University of the Basque Country, Bilbao, Spain
| | - Begoña Prieto
- Human Reproduction Unit, Cruces University Hospital, BioCruces, University of the Basque Country, Bilbao, Spain.,Instituto Valenciano de Infertilidad, IVI, Bilbao, Spain
| | - Felix Elortza
- Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Parque Tecnológico de Bizkaia, Derio, Spain
| | - Cristina Alonso
- OWL Metabolomics, Parque Tecnológico de Bizkaia, Derio, Spain
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Borges Jr. E, Montani DA, Setti AS, Zanetti BF, Figueira RDCS, Iaconelli Jr. A, Oliveira-Silva D, Braga DPDAF. Serum metabolites as predictive molecular markers of ovarian response to controlled stimulation: a pilot study. JBRA Assist Reprod 2019; 23:323-327. [PMID: 31173494 PMCID: PMC6798585 DOI: 10.5935/1518-0557.20190008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 12/10/2018] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVE This study aimed to look into the use of serum metabolites as potential biomarkers of response to controlled ovarian stimulation (COS) in patients undergoing intracytoplasmic sperm injection (ICSI) cycles. METHODS This case-control study analyzed serum samples from 30 patients aged <36 years undergoing COS for ICSI in a university-affiliated assisted reproduction center from January 2017 to August 2017. The samples were split into three groups based on response to COS as follows: poor responders: <4 retrieved oocytes (PR group, n=10); normal responders: ≥ 8 and ≤ 12 retrieved oocytes (NR group, n=10); and hyper-responders: >25 retrieved oocytes (HR, n=10). The metabolic profiles of the serum samples were compared between the groups through Principal Component Analysis (PCA). Receiver Operating Characteristic (ROC) curves were built to assess the power of the model at predicting response to COS. RESULTS PCA clearly distinguished between PR, NR and HR, and 10 ions were chosen as potential biomarkers of response to COS. These ions were more specific for PR than for NR. The ROC curve considering PR and NR had an area under the curve of 99.6% (95% CI: 88.9 - 100%). CONCLUSION The preliminary evidence discussed in this study suggests that serum metabolites may be used as predictive molecular markers of ovarian response to controlled stimulation. The integration of clinical and "omics" findings may allow the migration toward an era of personalized treatment in reproductive medicine.
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Affiliation(s)
- Edson Borges Jr.
- Fertility Medical Group. São Paulo, SP - Brazil
- Instituto Sapientiae - Centro de Estudos e Pesquisa em
Reprodução Assistida. São Paulo, SP - Brazil
| | - Daniela Antunes Montani
- Grupo de Bio-orgânica e Bioanalítica. Departamento de
Química - Instituto de Ciências Ambientais, Químicas e
Farmacêuticas – UNIFESP Diadema Campus, Diadema, SP - Brazil
| | - Amanda Souza Setti
- Fertility Medical Group. São Paulo, SP - Brazil
- Instituto Sapientiae - Centro de Estudos e Pesquisa em
Reprodução Assistida. São Paulo, SP - Brazil
| | - Bianca Ferrarini Zanetti
- Fertility Medical Group. São Paulo, SP - Brazil
- Instituto Sapientiae - Centro de Estudos e Pesquisa em
Reprodução Assistida. São Paulo, SP - Brazil
| | - Rita de Cássia Sávio Figueira
- Fertility Medical Group. São Paulo, SP - Brazil
- Instituto Sapientiae - Centro de Estudos e Pesquisa em
Reprodução Assistida. São Paulo, SP - Brazil
| | - Assumpto Iaconelli Jr.
- Fertility Medical Group. São Paulo, SP - Brazil
- Instituto Sapientiae - Centro de Estudos e Pesquisa em
Reprodução Assistida. São Paulo, SP - Brazil
| | - Diogo Oliveira-Silva
- Grupo de Bio-orgânica e Bioanalítica. Departamento de
Química - Instituto de Ciências Ambientais, Químicas e
Farmacêuticas – UNIFESP Diadema Campus, Diadema, SP - Brazil
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Ma N, Mochel NRD, Pham PD, Yoo TY, Cho KWY, Digman MA. Label-free assessment of pre-implantation embryo quality by the Fluorescence Lifetime Imaging Microscopy (FLIM)-phasor approach. Sci Rep 2019; 9:13206. [PMID: 31519916 PMCID: PMC6744410 DOI: 10.1038/s41598-019-48107-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 06/28/2019] [Indexed: 01/28/2023] Open
Abstract
Development of quantitative, safe and rapid techniques for assessing embryo quality provides significant advances in Assisted Reproductive Technologies (ART). Instead of assessing the embryo quality by the standard morphologic evaluation, we apply the phasor-FLIM (Fluorescence Lifetime Imaging Microscopy) method to capture endogenous fluorescent biomarkers of pre-implantation embryos as a non-morphological caliber for embryo quality. Here, we identify, under hypoxic and non-hypoxic conditions, the unique spectroscopic trajectories at different stages of mouse pre-implantation development, which is referred to as the developmental, or “D-trajectory”, that consists of fluorescence lifetime from different stages of mouse pre-implantation embryos. The D-trajectory correlates with intrinsic fluorescent species from a distinctive energy metabolism and oxidized lipids, as seen with Third Harmonic Generation (THG) that changes over time. In addition, we have defined a non-morphological Embryo Viability Index (EVI) to distinguish pre-implantation embryo quality using the Distance Analysis (DA), a machine learning algorithm to process the fluorescence lifetime distribution patterns. We show, under our experimental conditions, that the phasor-FLIM approach provides a much-needed non-invasive quantitative technology for identifying healthy embryos at the early compaction stage with 86% accuracy. The DA and phasor-FLIM method may provide the opportunity to improve implantation success rates for in vitro fertilization clinics.
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Affiliation(s)
- Ning Ma
- Department of Biomedical Engineering, University of California, Irvine, CA, USA.,Laboratory of Fluorescence Dynamics (LFD), University of California, Irvine, CA, USA
| | - Nabora Reyes de Mochel
- Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.,University of California San Francisco, School of Medicine, San Francisco, USA
| | - Paula Duyen Pham
- Department of Developmental and Cell Biology, University of California, Irvine, CA, USA
| | - Tae Yeon Yoo
- Department of Developmental and Cell Biology, University of California, Irvine, CA, USA
| | - Ken W Y Cho
- Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
| | - Michelle A Digman
- Department of Biomedical Engineering, University of California, Irvine, CA, USA. .,Laboratory of Fluorescence Dynamics (LFD), University of California, Irvine, CA, USA. .,Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
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Heidari F, Hosseini S, Yeganeh SM, Salehi M. Expression of miR-Let-7a, miR-15a, miR-16-1, and their target genes in fresh and vitrified embryos and its surrounding culture media for noninvasive embryo assessment. J Cell Biochem 2019; 120:19691-19698. [PMID: 31297859 DOI: 10.1002/jcb.29275] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 06/18/2019] [Indexed: 12/31/2022]
Abstract
microRNAs (miRNAs) play a critical role in implantation and development of mouse embryos. In this study, we aim to evaluate the possibility of miRNAs as potential biomarkers in the blastocyst culture to assess embryo quality. We also intend to investigate whether improved clinical outcomes of vitrified embryos agree with altered miRNA expressions. Mouse embryos from in vitro fertilization were vitrified at the two-cell stage. After thawing, the embryos were individually cultured and developed to the blastocyst stage. We used quantitative real-time polymerase chain reaction to evaluate miRNA expression levels in both vitrified and fresh groups, and culture medium (CM). The fibronectin binding assay was performed to examine for blastocyst attachment. The findings showed reduced expressions of miR-16-1 (0.2 ± 0.06) and miR-Let-7a (0.65 ± 0.1) after vitrification compared to fresh embryos. We observed significant upregulation of the target genes Vav3 (4.33 ± 0.25), integrin β-3 (Itg β3; 4.73 ± 0.2), and Bcl2 (2.29 ± 0.16) in the vitrified embryos compared to the fresh groups. Evaluation of blastocyst CM showed upregulation of miR-Let-7a (15.68 ± 0.89), miR-16-1 (16.18 ± 0.75), and miR-15a (13.36 ± 0.73) in the vitrified group in comparison to the fresh blastocysts (P < .05). The expression levels of miR-16-1 (3.28 ± 0.63), miR-15a (5.91 ± 0.38), and miR-Let-7a (9.07 ± 0.6) in CM of the vitrified blastocysts conducted on fibronectin were significantly higher than the fresh group (P < .05).This study showed that vitrification of embryos changes implantation and proliferation biomarkers. In addition, upregulated miRNAs in CM could be potentially used for noninvasive early assessment of embryo quality.
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Affiliation(s)
- Fezzeh Heidari
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Hosseini
- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,MOM Research Center, Tehran, Iran
| | - Samira M Yeganeh
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Salehi
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Liang B, Gao Y, Xu J, Song Y, Xuan L, Shi T, Wang N, Hou Z, Zhao YL, Huang WE, Chen ZJ. Raman profiling of embryo culture medium to identify aneuploid and euploid embryos. Fertil Steril 2019; 111:753-762.e1. [PMID: 30683589 DOI: 10.1016/j.fertnstert.2018.11.036] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 11/26/2018] [Accepted: 11/26/2018] [Indexed: 10/27/2022]
Abstract
OBJECTIVE To develop and validate Raman metabolic footprint analysis to determine chromosome euploidy and aneuploidy in embryos fertilized in vitro. DESIGN Retrospective study. SETTING Academic hospital. PATIENT(S) Unselected assisted reproductive technology population. INTERVENTION(S) To establish the analysis protocol, spent embryo culture medium samples with known genetic outcomes from 87 human embryos were collected and measured with the use of Raman spectroscopy. Individual Raman spectra were analyzed to find biologic components contributing to either euploidy or aneuploidy. To validate the protocol via machine-learning algorithms, additional 1,107 Raman spectra from 123 embryo culture media (61 euploidy and 62 aneuploidy) were analyzed. MAIN OUTCOME MEASURE(S) Raman-based footprint profiling of spent culture media and preimplantation genetic testing for aneuploidy (PGT-A). RESULT(S) Mean-centered Raman spectra and principal component analysis showed differences in the footprints of euploid and aneuploid embryos growing in culture medium. Significant differences in Raman bands associated with small RNAs and lipids were also observed. Stacking classification based on k-nearest-neighbor, random forests, and extreme-gradient-boosting algorithms achieved an overall accuracy of 95.9% in correctly assigning either euploidy or aneuploidy based on Raman spectra, which was validated by PGT-A sequencing results. CONCLUSION(S) This study suggests that chromosomal abnormalities in embryos should lead to changes of metabolic footprints in embryo growth medium that can be detected by Raman spectroscopy. The ploidy status of embryos was analyzed by means of Raman-based footprint profiling of spent culture media and was consistent with PGT-A testing performed by next-generation sequencing.
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Affiliation(s)
- Bo Liang
- State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Yuan Gao
- Center for Reproductive Medicine, Provincial Hospital Affiliated with Shandong University, Jinan, Shandong, China; Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, Shandong, China
| | - Jiabao Xu
- Department of Engineering Science, University of Oxford, Oxford, United Kingdom
| | - Yizhi Song
- Department of Engineering Science, University of Oxford, Oxford, United Kingdom
| | - Liming Xuan
- Basecare Medical Device Co., Suzhou, Jiangsu, China
| | - Ting Shi
- State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Ning Wang
- Mathematical Institute, University of Oxford, Oxford, United Kingdom
| | - Zhaoxu Hou
- Mathematical Institute, University of Oxford, Oxford, United Kingdom
| | - Yi-Lei Zhao
- State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
| | - Wei E Huang
- Department of Engineering Science, University of Oxford, Oxford, United Kingdom
| | - Zi-Jiang Chen
- Center for Reproductive Medicine, Provincial Hospital Affiliated with Shandong University, Jinan, Shandong, China; Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, Shandong, China
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Bielfeld AP, Pour SJ, Poschmann G, Stühler K, Krüssel JS, Baston-Büst DM. A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level⁻Does hCG Render the Endometrium of RIF Patients? Int J Mol Sci 2019; 20:ijms20020425. [PMID: 30669470 PMCID: PMC6358950 DOI: 10.3390/ijms20020425] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 01/16/2019] [Accepted: 01/17/2019] [Indexed: 12/21/2022] Open
Abstract
Background: The molecular signature of endometrial receptivity still remains barely understood, especially when focused on the possible benefit of therapeutical interventions and implantation-related pathologies. Therefore, the protein composition of tissue and isolated primary cells (endometrial stromal cells, ESCs) from endometrial scratchings of ART (Assisted Reproductive Techniques) patients with repeated implantation failure (RIF) was compared to volunteers with proven fertility during the time of embryo implantation (LH + 7). Furthermore, an analysis of the endometrial tissue of fertile women infused with human chorionic gonadotropin (hCG) was conducted. Methods: Endometrial samples (n = 6 RIF, n = 10 fertile controls) were split into 3 pieces: 1/3 each was frozen in liquid nitrogen, 1/3 fixed in PFA and 1/3 cultured. Protein lysates prepared from fresh frozen tissue were processed for mass spectrometric analysis. Results: Three proteins (EPPK1, BCLAF1 and PTMA) showed a statistically altered abundance in the endometrial tissue of RIF patients. Furthermore, pathways like metabolism, immune system, ferroptosis and the endoplasmic reticulum were altered in RIF patients. Remarkably, endometrial tissues of RIF patients showed a significantly higher (p-value = 9 × 10−8) protein intensity correlation (Pearson’s correlation coefficient = 0.95) compared to fertile women (Pearson’s correlation coefficient = 0.88). The in vivo infusion of hCG stimulated proteins of endocytosis, HIF1 signalling and chemokine production. Notably, patients suffering from RIF had a clinical pregnancy rate of 19% after the intrauterine infusion of hCG before embryo transfer (ET) compared to their failed previous cycles. Conclusion: Our study showed for the first time that the endometrial proteome composition of RIF patients differs from fertile controls during the window of implantation. The intrauterine infusion of hCG prior to an embryo transfer might improve the chemokine triggered embryo-endometrial dialogue and intensify the angiogenesis and immune response. From a clinical point of view, the hCG infusion prior to an embryo transfer might increase the pregnancy rate of RIF patients.
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Affiliation(s)
- Alexandra P Bielfeld
- Medical Center University of Düsseldorf, Department of OB/GYN and REI (UniKiD), Moorenstrasse 5, 40225 Düsseldorf, Germany.
| | - Sarah Jean Pour
- Medical Center University of Düsseldorf, Department of OB/GYN and REI (UniKiD), Moorenstrasse 5, 40225 Düsseldorf, Germany.
| | - Gereon Poschmann
- Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
| | - Kai Stühler
- Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
- Institute for Molecular Medicine, University Hospital Düsseldorf, 40225 Düsseldorf, Germany.
| | - Jan-Steffen Krüssel
- Medical Center University of Düsseldorf, Department of OB/GYN and REI (UniKiD), Moorenstrasse 5, 40225 Düsseldorf, Germany.
| | - Dunja M Baston-Büst
- Medical Center University of Düsseldorf, Department of OB/GYN and REI (UniKiD), Moorenstrasse 5, 40225 Düsseldorf, Germany.
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Li XX, Cao PH, Han WX, Xu YK, Wu H, Yu XL, Chen JY, Zhang F, Li YH. Non-invasive metabolomic profiling of culture media of ICSI- and IVF-derived early developmental cattle embryos via Raman spectroscopy. Anim Reprod Sci 2018; 196:99-110. [DOI: 10.1016/j.anireprosci.2018.07.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 06/18/2018] [Accepted: 07/02/2018] [Indexed: 10/28/2022]
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Li X, Yin M, Gu J, Hou Y, Tian F, Sun F. Metabolomic Profiling of Plasma Samples from Women with Recurrent Spontaneous Abortion. Med Sci Monit 2018; 24:4038-4045. [PMID: 29898462 PMCID: PMC6031124 DOI: 10.12659/msm.907653] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background Gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS) metabolomics have been deployed to detect novel differential metabolites in cases with recurrent spontaneous abortion (RSA). Material/Methods Fifty patients who had recurrent spontaneous abortions (RSAs) and 51 control patients (age, gestational age, and body mass index (BMI) match) were enrolled in this study. Untargeted GC-MS and targeted LC-MS were combined to discover and validate the different metabolomic profiles between groups. Score plots of orthogonal partial least-squares discriminant analysis (OPLS-DA) clearly separated the RSA group from the control group. The variable importance in projection (VIP) generated in OPLS-DA processing represented the contribution to the discrimination of each metabolite ion between groups. Variables with a VIP >1 and P<0.05 were considered to be different variables. We also used MetaboAnalyst 3.0 to analyze the pathway impact of potential metabolite biomarkers. Results Fifty-four metabolites were significantly different between the two groups, as indicated by a VIP >1 and P<0.05. The metabolic pathways involving glycine, serine, threonine (P=0.00529, impact=0.26), beta-alanine (P=0.0284, impact=0.27), and phenylalanine metabolism (P=0.0217, impact=0.17), along with the tricarboxylic acid (TCA) cycle (P=0.0113, impact=0.19) and the glycolysis pathway (P=0.037, impact=0.1) are obviously related to RSA. Verification by LC-MS showed that the concentration of lactic acid in RSA was higher than that in the control group (P<0.05), while the concentration of 5-methoxytryptamine was significantly lower in the RSA group (P<0.05). Conclusions In our study, untargeted GC-MS was used to detect disturbance of metabolism occurs in RSA and targeted LC-MS further was used to show that plasma concentrations of two metabolites (lactic acid and 5-methoxytryptamine) were different in the RSA compared to the control group.
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Affiliation(s)
- XiaoCui Li
- Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai, China (mainland)
| | - MingHong Yin
- Department of Gynecology and Obstetrics, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai, China (mainland)
| | - JinPing Gu
- Department of Gynecology and Obstetrics, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai, China (mainland)
| | - YanYan Hou
- Department of Gynecology and Obstetrics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - FuJu Tian
- Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai, China (mainland)
| | - Feng Sun
- Department of Gynecology and Obstetrics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
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Metabolism of the oocyte and the preimplantation embryo: implications for assisted reproduction. Curr Opin Obstet Gynecol 2018; 30:163-170. [DOI: 10.1097/gco.0000000000000455] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Siristatidis CS, Sertedaki E, Vaidakis D, Varounis C, Trivella M. Metabolomics for improving pregnancy outcomes in women undergoing assisted reproductive technologies. Cochrane Database Syst Rev 2018; 3:CD011872. [PMID: 29547689 PMCID: PMC6494410 DOI: 10.1002/14651858.cd011872.pub3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND In order to overcome the low effectiveness of assisted reproductive technologies (ART) and the high incidence of multiple births, metabolomics is proposed as a non-invasive method to assess oocyte quality, embryo viability, and endometrial receptivity, and facilitate a targeted subfertility treatment. OBJECTIVES To evaluate the effectiveness and safety of metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity for improving live birth or ongoing pregnancy rates in women undergoing ART, compared to conventional methods of assessment. SEARCH METHODS We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL and two trial registers (Feburary 2018). We also examined the reference lists of primary studies and review articles, citation lists of relevant publications, and abstracts of major scientific meetings. SELECTION CRITERIA Randomised controlled trials (RCTs) on metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity in women undergoing ART. DATA COLLECTION AND ANALYSIS Pairs of review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary outcomes were rates of live birth or ongoing pregnancy (composite outcome) and miscarriage. Secondary outcomes were clinical pregnancy, multiple and ectopic pregnancy, cycle cancellation, and foetal abnormalities. We combined data to calculate odds ratios (ORs) for dichotomous data and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. MAIN RESULTS We included four trials with a total of 924 women, with a mean age of 33 years. All assessed the role of metabolomic investigation of embryo viability. We found no RCTs that addressed the metabolomic assessment of oocyte quality or endometrial receptivity.We found low-quality evidence of little or no difference between metabolomic and non-metabolomic assessment of embryos for rates of live birth or ongoing pregnancy (OR 1.02, 95% CI 0.77 to 1.35, I² = 0%; four RCTs; N = 924), live birth alone (OR 0.99, 95% CI 0.69 to 1.44, I² = 0%; three RCTs; N = 597), or miscarriage (OR 1.18, 95% CI 0.77 to 1.82; I² = 0%; three RCTs; N = 869). A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for live birth or ongoing pregnancy (OR 0.90, 95% CI 0.66 to 1.25, I² = 0%; two RCTs; N = 744). Our findings suggested that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics.We found low-quality evidence of little or no difference between groups in rates of clinical pregnancy (OR 1.11, 95% CI 0.85 to 1.45; I²= 44%; four trials; N = 924) or multiple pregnancy (OR 1.50, 95% CI 0.70 to 3.19; I² = 0%; two RCTs, N = 180). Rates of cycle cancellation were higher in the metabolomics group (OR 1.78, 95% CI 1.18 to 2.69; I² = 51%; two RCTs; N = 744, low quality evidence). There was very low-quality evidence of little or no difference between groups in rates of ectopic pregnancy rates (OR 3.00, 95% CI 0.12 to 74.07; one RCT; N = 417), and foetal abnormality (no events; one RCT; N = 125). Data were lacking on other adverse effects. A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for clinical pregnancy (OR 1.03, 95% CI 0.76 to 1.38; I² = 40%; two RCTs; N = 744).The overall quality of the evidence ranged from very low to low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting, and other biases), imprecision, and inconsistency across trials. AUTHORS' CONCLUSIONS According to current trials in women undergoing ART, there is no evidence to show that metabolomic assessment of embryos before implantation has any meaningful effect on rates of live birth, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy or foetal abnormalities. The existing evidence varied from very low to low-quality. Data on other adverse events were sparse, so we could not reach conclusions on these. At the moment, there is no evidence to support or refute the use of this technique for subfertile women undergoing ART. Robust evidence is needed from further RCTs, which study the effects on live birth and miscarriage rates for the metabolomic assessment of embryo viability. Well designed and executed trials are also needed to study the effects on oocyte quality and endometrial receptivity, since none are currently available.
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Affiliation(s)
- Charalampos S Siristatidis
- Medical School, National and Kapodistrian University of AthensAssisted Reproduction Unit, 3rd Department of Obstetrics and GynaecologyAttikon University HospitalRimini 1AthensChaidariGreece12462
| | - Eleni Sertedaki
- Medical School, National and Kapodistrian University of Athens75 M. Assias StreetGoudiAthensGreece115 27
| | - Dennis Vaidakis
- University of Athens3rd Department of Obstetrics and Gynecology'Attikon' Hospital, ChaidariAthensGreece
| | - Christos Varounis
- Attikon University Hospital2nd Department of Cardiology, University of Athens Medical SchoolRimini 1HaidariAthensGreece12462
| | - Marialena Trivella
- University of OxfordCentre for Statistics in MedicineBotnar Research CentreWindmill RoadOxfordUKOX3 7LD
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Miao X, Xiao B, Shui S, Yang J, Huang R, Dong J. Metabolomics analysis of serum reveals the effect of Danggui Buxue Tang on fatigued mice induced by exhausting physical exercise. J Pharm Biomed Anal 2018; 151:301-309. [PMID: 29413978 DOI: 10.1016/j.jpba.2018.01.028] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 01/12/2018] [Accepted: 01/15/2018] [Indexed: 02/07/2023]
Abstract
Danggui Buxue Tang (DBT), believed to invigorate 'Qi' (vital energy) and nourish 'Blood' (body circulation), is a traditional Chinese medicine formula. In this study, a metabolomics approach with gas chromatography coupled to mass spectrometry combined with pattern recognition was adopted to investigate the underlying mechanism of the antifatigue effect of DBT on fatigue of mice induced by weight-loaded forced swimming. Fourteen endogenous metabolites, up-regulated or down-regulated, were identified in the model mice by analysis tools of partial least-squares discriminant analysis (PLS-DA) and XCMS online software. Furthermore, the metabolites were reversed by DBT treatment, offering evidence for the antifatigue effect. In addition, intervention of DBT changed the levels of biochemical parameters. DBT showed obvious efficacy on the fatigued mice possibly by regulating the pathways of phenylalanine, tyrosine and tryptophan metabolism, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylate metabolism, pyruvate metabolism, and TCA cycle. This study demonstrated that DBT has a good antifatigue effect and that metabolomics is a powerful means to gain insights into the therapeutic effect of traditional Chinese medicine formulas.
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Affiliation(s)
- Xiaoyao Miao
- Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China
| | - Bingkun Xiao
- Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China
| | - Sufang Shui
- Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China
| | - Jianyun Yang
- Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China
| | - Rongqing Huang
- Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
| | - Junxing Dong
- Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
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Sepulveda-Rincon LP, Islam N, Marsters P, Campbell BK, Beaujean N, Maalouf WE. Embryo cell allocation patterns are not altered by biopsy but can be linked with further development. Reproduction 2017; 154:807-814. [PMID: 28971891 PMCID: PMC5747100 DOI: 10.1530/rep-17-0514] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 08/15/2017] [Accepted: 09/28/2017] [Indexed: 11/08/2022]
Abstract
It has been suggested that first embryo cleavage can be related with the embryonic-abembryonic axis at blastocyst stage in mice. Thus, cells of the 2-cell embryo might be already biased to form the inner cell mass or trophectoderm. This study was conducted to observe the possible effects of embryo biopsy on cell allocation patterns during embryo preimplantation in two different mouse strains and the effects of these patterns on further development. First, one blastomere of the 2-cell embryo was injected with a lipophilic tracer and cell allocation patterns were observed at blastocyst stage. Blastocysts were classified into orthogonal, deviant or random pattern. For the first experiment, embryos were biopsied at 8-cell stage and total cell counts (TCC) were annotated. Furthermore, non-biopsied blastocysts were transferred into foster mothers. Then, pups and their organs were weighed two weeks after birth. Random pattern was significantly recurrent (≈60%), against orthogonal (<22%) and deviant (<22%) patterns among groups. These patterns were not affected by biopsy procedure. However, TCC on deviant embryos were reduced after biopsy. Moreover, no differences were found between patterns for implantation rates, litter size, live offspring and organ weights (lungs, liver, pancreas and spleen). However, deviant pups presented heavier hearts and orthogonal pups presented lighter kidneys among the group. In conclusion, these results suggest that single blastomere removal does not disturb cell allocation patterns during pre-implantation. Nonetheless, the results suggest that embryos following different cell allocation patterns present different coping mechanisms against in vitro manipulations and further development might be altered.
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Affiliation(s)
- L P Sepulveda-Rincon
- Division of Child HealthObstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK
| | - N Islam
- Division of Child HealthObstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK
| | - P Marsters
- Division of Child HealthObstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK
| | - B K Campbell
- Division of Child HealthObstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK
| | - N Beaujean
- Univ LyonUniversité Claude Bernard Lyon 1, Inserm, INRA, Stem Cell and Brain Research Institute U1208, USC1361, 69500 Bron, France
| | - W E Maalouf
- Division of Child HealthObstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK
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Improvement of pregnancy outcome by extending embryo culture in IVF-ET during clinical application. J Assist Reprod Genet 2017; 35:321-329. [PMID: 29124461 DOI: 10.1007/s10815-017-1065-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 10/05/2017] [Indexed: 12/21/2022] Open
Abstract
PURPOSE The purpose of this study is to investigate the application value of the extended embryo culture for 7-8 h in day 3 morning during IVF-ET process. METHODS Embryos were retrospectively assessed during 08:00-09:00 on the morning of day 3 in the control group, and were assessed once again at 16:00 in the afternoon in the extended culture (EC) group. The embryos with good developmental potential were preferentially selected to transfer. The cumulative pregnancy outcomes were analyzed in one oocyte retrieval cycle. RESULTS Similar proportions were found in the rates of cumulative clinical pregnancy, cumulative live birth, and the perinatal/neonatal outcomes per oocyte retrieval cycle (P > 0.05). But higher total clinical pregnancy rate, higher total implantation rate, and lower total abortion rate were obtained in the EC group (P < 0.05). After EC, 53.58% of the embryos were able to continue to develop. The transferred embryos were mainly composed of ≥ 8-cell embryos (75.90%) in the EC group and ≤ 8-cell embryos (82.92%) in the control group. Interestingly, the implantation rates were increasingly improved with the increasing blastomere number up to 56.31% at the morula stage in the EC group, while they were limited to 32.33% at 8-cell stage in the control group. CONCLUSIONS The extended culture of day 3 embryos for 7-8 h not only reduced the risk of IVF-ET treatment compared to blastocyst culture through another 2-3 days, but also improved the clinical outcomes and the efficiency of every transferred cycle and every transferred embryo.
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Spent culture medium analysis from individually cultured bovine embryos demonstrates metabolomic differences. ZYGOTE 2017; 25:662-674. [PMID: 29032784 DOI: 10.1017/s0967199417000417] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Spent culture medium can provide valuable information regarding the physiological state of a bovine preimplantation embryos through non-invasive analysis of the sum/depleted metabolite constituents. Metabolomics has become of great interest as an adjunct technique to morphological and cleavage-rate assessment, but more importantly, in improving our understanding of metabolism. In this study, in vitro produced bovine embryos developing at different rates were evaluated using proton nuclear magnetic resonance (1H NMR). Spent culture medium from individually cultured embryos (2-cell to blastocyst stage) were divided into two groups based on their cleavage rate fast growing (FG) and slow growing (SG; developmentally delayed by 12-24 h), then analyzed by a 600 MHz NMR spectrometer. Sixteen metabolites were detected and investigated for sum/depletion throughout development. Data indicate distinct differences between the 4-cell SG and FG embryos for pyruvate (P < 0.05, n = 9) and at the 16-cell stage for acetate, tryptophan, leucine/isoleucine, valine and histidine. Overall sum/depletion levels of metabolites demonstrated that embryos produced glutamate, but consumed histidine, tyrosine, glycine, methionine, tryptophan, phenylalanine, lysine, arginine, acetate, threonine, alanine, pyruvate, valine, isoleucine/leucine, and lactate with an overall trend of higher consumption of these metabolites by FG groups. Principal component analysis revealed distinct clustering of the plain medium, SG, and FG group, signifying the uniqueness of the metabolomic signatures of each of these groups. This study is the first of its kind to characterize the metabolomic profiles of SG and FG bovine embryos produced in vitro using 1H NMR. Elucidating differences between embryos of varying developmental rates could contribute to a better understanding of embryonic health and physiology.
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