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Tain YL, Huang LT, Hsu CN. Developmental Programming of Adult Disease: Reprogramming by Melatonin? Int J Mol Sci 2017; 18:ijms18020426. [PMID: 28212315 PMCID: PMC5343960 DOI: 10.3390/ijms18020426] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 01/26/2017] [Accepted: 02/13/2017] [Indexed: 12/25/2022] Open
Abstract
Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the "developmental origins of health and disease" (DOHaD) or "developmental programming". The DOHaD concept offers the "reprogramming" strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs.
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Affiliation(s)
- You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
| | - Li-Tung Huang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
- Department of Traditional Chinese Medicine, Chang Gung University, Linkow 244, Taiwan.
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
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Merchant NM, Azzopardi DV, Edwards AD. Neonatal hypoxic ischaemic encephalopathy: current and future treatment options. Expert Opin Orphan Drugs 2015. [DOI: 10.1517/21678707.2015.1021776] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Ouzir M, Bouhaddou N, Khalki H, Lakhdar-Ghazal N. Physiological and pharmacological properties of 5-methoxytryptophol. Expert Rev Endocrinol Metab 2013; 8:355-364. [PMID: 30736152 DOI: 10.1586/17446651.2013.811866] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
5-methoxytryptophol (5-ML) is a pineal indoleamine derived from serotonin shown to be biologically active in a number of species. This indolamine exhibits a circadian pattern synchronized with the day-night cycle with significant increases during daylight, already recognized in vertebrates. The multiplicity of physiological and endocrine functions of 5-ML is remarkable; it is involved in circadian rhythms, reproduction and sexual processes. Furthermore, a number of pharmacological benefits of 5-ML have been reported, including immunomodulatory, antitumor and antioxidative activities. However, the molecular mechanisms of these pharmacological effects remain unclear. The purpose of this article is to provide an overview on the general properties and physiological functions of 5-ML. An attempt has been made to fully document all studies performed using 5-ML. In addition, this article aims to gain insight into the current state of knowledge regarding pharmacological and therapeutic effects of this indoleamine.
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Affiliation(s)
- Mounir Ouzir
- a Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco.
| | - Nezha Bouhaddou
- b Unit of Research on Biological Rhythms and Environment, Faculty of Sciences University Mohammed V, Rabat, Morocco
| | - Hanane Khalki
- c Department of Biology, Laboratory of Pharmacology, Neurobiology and Behavior, Faculty of Sciences Semlalia University Cady Ayyad, Marrakech, Morocco
| | - Nouria Lakhdar-Ghazal
- b Unit of Research on Biological Rhythms and Environment, Faculty of Sciences University Mohammed V, Rabat, Morocco
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Bai J, Dong L, Song Z, Ge H, Cai X, Wang G, Liu P. The role of melatonin as an antioxidant in human lens epithelial cells. Free Radic Res 2013; 47:635-42. [DOI: 10.3109/10715762.2013.808743] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Supplementation with low concentrations of melatonin improves nuclear maturation of human oocytes in vitro. J Assist Reprod Genet 2013; 30:933-8. [PMID: 23737216 DOI: 10.1007/s10815-013-0021-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2013] [Accepted: 05/24/2013] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Studies in bovine and porcine have indicated that melatonin (MT) could induce meiotic maturation of immature oocytes in vitro. The object of the current study was to investigate if MT could ameliorate human oocytes maturation during rescue in vitro maturation (IVM). METHODS Two hundred seventy eight germinal vesicle (GV) oocytes and 451 (MI) metaphase I oocytes were vitrified, thawed and then matured in vitro. All the oocytes were randomly allocated into six groups in which the oocytes were cultured in medium supplemented with different concentrations of MT (0, 10(-2), 1, 10(2), 10(4), 10(6) nM) and nuclear maturation was evaluated at 6 h, 12 h, 18 h, 24 h and 48 h of culture. RESULTS The optimal MT concentration for both GV and MI oocytes was 1 nM. At 24 h of culture, nuclear maturation rate of MI oocytes cultured in 1 nM MT medium was significantly higher than other groups (P < 0.05); Nuclear maturation rate of GV oocytes cultured in 1 nM MT medium was also significantly higher than the control group (P < 0.05). On the other hand, decreased nuclear maturation rate was observed in the high MT concentration group (10(6) nM). CONCLUSIONS The current study demonstrated that low concentration of exogenous MT could ameliorate nuclear maturation of human oocyte during rescue IVM, while high concentration of MT presented negative effects.
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Lampiao F, Du Plessis SS. New developments of the effect of melatonin on reproduction. World J Obstet Gynecol 2013; 2:8-15. [DOI: 10.5317/wjog.v2.i2.8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Revised: 04/18/2013] [Accepted: 05/10/2013] [Indexed: 02/05/2023] Open
Abstract
In the past decades, a lot of advances in understanding the biochemistry and physiology of the pineal gland have been made. There is evidence that it interacts with many endocrine as well as non-endocrine tissues to influence their metabolic activity modulating many organs and functions. Melatonin is secreted by the pineal gland in the brain and plays an important role in regulating the neuroendocrine system. This hormone is one of the major role players in the regulation of the circadian sleep-wake cycle. It is normally released from the pineal gland during the night in response to environmental changes in light. Studies have shown that melatonin plays a role in the regulation of many reproductive processes such as puberty, gonadal function, and pregnancy. Beside these, melatonin has been shown to be able to directly neutralize a number of free radicals and reactive oxygen and nitrogen species. The main objective of this review is to provide comprehensive information about the new developments in melatonin research regarding its role in reproduction. A review of international scientific literature was done and a question-and-answer format was used in an attempt to convey comprehensive information in a simple manner. This review discusses evidence currently available relating to the effect of melatonin on reproductive processes. It deliberates the mechanism of action of melatonin, its effect on puberty, testicular and ova function, pregnancy, and oxidative stress. A growing body of scientific evidence is suggesting that melatonin plays an important role in reproductive function. It is therefore imperative to highlight the beneficial effects of this hormone in improving the reproductive processes.
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Chen YC, Sheen JM, Tiao MM, Tain YL, Huang LT. Roles of melatonin in fetal programming in compromised pregnancies. Int J Mol Sci 2013; 14:5380-401. [PMID: 23466884 PMCID: PMC3634509 DOI: 10.3390/ijms14035380] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2013] [Revised: 02/25/2013] [Accepted: 02/25/2013] [Indexed: 12/24/2022] Open
Abstract
Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms.
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Affiliation(s)
- Yu-Chieh Chen
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; E-Mails: (Y.-C.C.); (J.-M.S.); (M.-M.T.); (Y.-L.T.)
| | - Jiunn-Ming Sheen
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; E-Mails: (Y.-C.C.); (J.-M.S.); (M.-M.T.); (Y.-L.T.)
| | - Miao-Meng Tiao
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; E-Mails: (Y.-C.C.); (J.-M.S.); (M.-M.T.); (Y.-L.T.)
| | - You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; E-Mails: (Y.-C.C.); (J.-M.S.); (M.-M.T.); (Y.-L.T.)
- Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Li-Tung Huang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; E-Mails: (Y.-C.C.); (J.-M.S.); (M.-M.T.); (Y.-L.T.)
- Department of Traditional Chinese Medicine, Chang Gung University, Linkow 333, Taiwan
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +886-975-056-169; Fax: +886-773-380-09
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Tamura H, Takasaki A, Taketani T, Tanabe M, Kizuka F, Lee L, Tamura I, Maekawa R, Asada H, Yamagata Y, Sugino N. Melatonin as a free radical scavenger in the ovarian follicle. Endocr J 2013; 60:1-13. [PMID: 23171705 DOI: 10.1507/endocrj.ej12-0263] [Citation(s) in RCA: 134] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
This review summarizes new findings related to beneficial effects of melatonin (N-acetyl-5-methoxytryptamine) on reproductive physiology. Recently many researchers have begun to study the local role of melatonin as an antioxidant. We focused on intra-follicular role of melatonin in the ovary. Melatonin, secreted by the pineal gland, is taken up into the follicular fluid from the blood. Reactive oxygen species (ROS) are produced within the follicles, during the ovulatory process. Melatonin reduces oxidative stress as an antioxidant, and contribute to oocyte maturation, embryo development and luteinization of granulosa cells. Our clinical study demonstrated that melatonin treatment for infertile women increases intra-follicular melatonin concentrations, reduces intra-follicular oxidative damage, and elevates fertilization and pregnancy rates. Melatonin treatment also improves progesterone production by corpus luteum in infertile women with luteal phase defect. Melatonin treatment could become a new cure for improving oocyte quality and luteal function in infertile women.
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Affiliation(s)
- Hiroshi Tamura
- Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
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Tamura H, Takasaki A, Taketani T, Tanabe M, Kizuka F, Lee L, Tamura I, Maekawa R, Aasada H, Yamagata Y, Sugino N. The role of melatonin as an antioxidant in the follicle. J Ovarian Res 2012; 5:5. [PMID: 22277103 PMCID: PMC3296634 DOI: 10.1186/1757-2215-5-5] [Citation(s) in RCA: 157] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 01/26/2012] [Indexed: 12/12/2022] Open
Abstract
Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at night by pineal gland, and it regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It has been believed that melatonin regulates ovarian function by the regulation of gonadotropin release in the hypothalamus-pituitary gland axis via its specific receptors. In addition to the receptor mediated action, the discovery of melatonin as a direct free radical scavenger has greatly broadened the understanding of melatonin's mechanisms which benefit reproductive physiology. Higher concentrations of melatonin have been found in human preovulatory follicular fluid compared to serum, and there is growing evidence of the direct effects of melatonin on ovarian function especially oocyte maturation and embryo development. Many scientists have focused on the direct role of melatonin on oocyte maturation and embryo development as an anti-oxidant to reduce oxidative stress induced by reactive oxygen species, which are produced during ovulation process. The beneficial effects of melatonin administration on oocyte maturation and embryo development have been confirmed by in vitro and in vivo experiments in animals. This review also discusses the first application of melatonin to the clinical treatment of infertile women and confirms that melatonin administration reduces intrafollicular oxidative damage and increase fertilization rates. This review summarizes our recent works and new findings related to the reported beneficial effects of melatonin on reproductive physiology in its role as a reducer of oxidative stress, especially on oocyte maturation and embryo development.
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Affiliation(s)
- Hiroshi Tamura
- Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505 Japan.
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Khaksary Mahabady M, Najafzadeh Varzi H, Bakhtiari E. The effects of cyclophosphamide, melatonin and carvedilol on neural tube and skeletal system of mice fetuses in prenatal period. Ann Anat 2011; 193:459-65. [DOI: 10.1016/j.aanat.2011.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Revised: 04/17/2011] [Accepted: 05/05/2011] [Indexed: 11/17/2022]
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Aversa S, Pellegrino S, Barberi I, Reiter RJ, Gitto E. Potential utility of melatonin as an antioxidant during pregnancy and in the perinatal period. J Matern Fetal Neonatal Med 2011; 25:207-21. [PMID: 21557691 DOI: 10.3109/14767058.2011.573827] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Reactive oxygen species (ROS) play a critical role in the pathogenesis of various diseases during pregnancy and the perinatal period. Newborns are more prone to oxidative stress than individuals later in life. During pregnancy, increased oxygen demand augments the rate of production of ROS and women, even during normal pregnancies, experience elevated oxidative stress compared with non-pregnant women. ROS generation is also increased in the placenta during preeclampsia. Melatonin is a highly effective direct free-radical scavenger, indirect antioxidant, and cytoprotective agent in human pregnancy and it appears to be essential for successful pregnancy. This suggests a role for melatonin in human reproduction and in neonatal pathologies (asphyxia, respiratory distress syndrome, sepsis, etc.). This review summarizes current knowledge concerning the role for melatonin in human pregnancy and in the newborn. Numerous studies agree that short-term melatonin therapy is highly effective in reducing complications during pregnancy and in the neonatal period. No significant toxicity or treatment-related side effects with long-term melatonin therapy in children and adults have been reported. Treatment with melatonin might result in a wide range of health benefits, including improved quality of life and reduced healthcare costs.
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Affiliation(s)
- Salvatore Aversa
- Neonatal Intensive Care Unit, Department of Pediatrics, University of Messina, Italy
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Abstract
Melatonin, an endogenously produced indoleamine, is a highly effective antioxidant, free radical scavenger, and a primary circadian regulator. Melatonin has important antioxidant properties owing to direct and indirect effects. It directly scavenges reactive oxygen and reactive nitrogen species, prevents molecular oxidation, improves mitochondrial physiology, and restores glutathione homeostasis. Its indirect antioxidant effects stem from its ability to stimulate the activities of the enzymes involved in the glutathione cycling and production. Melatonin, by reducing free radical damage, may be an effective protective agent for the fetus as it is in adults. Several clinical studies on melatonin have shown that it reduces oxidative stress in human newborns with sepsis, hypoxic distress, or other conditions, where there is excessive free radical generation. A role of melatonin in infant development has also been suggested. Pineal dysfunction may be associated with deleterious outcomes in infants and may contribute to an increased prevalence of sudden infant death syndrome. Delayed melatonin production is evident in infants who had experienced an apparent life-threatening event. Melatonin has been used as a pharmacologic treatment for insomnias associated with shift work, jet lag, and delayed sleep onset in adults for decades. In children as well, melatonin has value as a sleep-promoting agent. Evidence suggests that melatonin has utility as an analgesic agent presumably related to its ability to release β-endorphin. The data support the notion that melatonin, or one of its analogs, might find use as an anesthetic agent in children.
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Affiliation(s)
- Eloisa Gitto
- Neonatal Intensive Care Unit, Department of Pediatrics, University of Messina, Messina, Italy.
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Choe C, Shin YW, Kim EJ, Cho SR, Kim HJ, Choi SH, Han MH, Han J, Son DS, Kang D. Synergistic effects of glutathione and β-mercaptoethanol treatment during in vitro maturation of porcine oocytes on early embryonic development in a culture system supplemented with L-cysteine. J Reprod Dev 2010; 56:575-82. [PMID: 20657156 DOI: 10.1262/jrd.09-214h] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Various methods have been used to remove reactive oxygen species (ROS) generated from in vitro culture (IVC) conditions that can cause cell injury or death, including the application of low oxygen (O(2)) tension and the addition of antioxidants. The beneficial effects of antioxidants and O(2) tension on IVC of porcine embryos, however, are controversial among researchers. In this study, we sought to determine the effects and optimal concentrations of antioxidants for the development of porcine embryos in an IVC system. Specifically, we examined the synergistic effects of antioxidants on development to the blastocyst stage in a culture system supplemented with L-cysteine during IVM. Of the antioxidants tested (melatonin, glutathione (GSH), β-mercaptoethanol (β-ME), N-acetylcysteine (NAC) and dithiothreitol (DTT)), addition of GSH (1 mM) or β-ME (25 µM) significantly increased development to the blastocyst stage compared with the controls without antioxidant treatment (22.2 ± 4.2% for 1 mM GSH, 25.9 ± 2.2% for 25 µM β-ME and 12-13% for the control, P<0.05). In addition, the mean cell number per blastocyst was increased by approximately 1.7-fold in the presence of GSH or β -ME. These GSH- and β-ME-induced increases in development to the blastocyst stage and total cell number, however, were not mimicked by melatonin, NAC or DTT, all of which are ROS scavengers. The combination of GSH or β-ME with L-cysteine significantly reduced high O(2) tension-induced ROS production (P<0.05). These results suggest that a combination of 1 mM GSH or 25 µM β-ME with 1 mM L-cysteine could be used for production of high quality porcine blastocysts in IVC systems.
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Affiliation(s)
- Changyong Choe
- Republic of Korea Animal Genetic Resources Station, National Institute of Animal Science, RDA, Namwon, Korea
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Shi JM, Tian XZ, Zhou GB, Wang L, Gao C, Zhu SE, Zeng SM, Tian JH, Liu GS. Melatonin exists in porcine follicular fluid and improves in vitro maturation and parthenogenetic development of porcine oocytes. J Pineal Res 2009; 47:318-23. [PMID: 19817971 DOI: 10.1111/j.1600-079x.2009.00717.x] [Citation(s) in RCA: 144] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
This study focused on the effect of melatonin on in vitro maturation of porcine oocytes and their parthenogenetic embryonic development. Melatonin was measured in porcine follicular fluid of follicles of different sizes in the same ovary. Melatonin exists in follicular fluid, and the concentration is approximately 10(-11) m. Its concentration decreased as the diameter of follicle increased, which suggests an effect of melatonin on oocyte maturation. Therefore, immature oocytes were cultured in vitro in maturation medium supplemented with melatonin (10(-11), 10(-9), 10(-7), 10(-5) and 10(-3) m) or without melatonin. The oocytes at maturation stage were collected and activated. The parthenogenetic embryos were cultured and observed in medium supplemented with or without melatonin. Fresh immature oocytes without melatonin treatment were used as control. When only maturation medium was supplemented with 10(-9) m melatonin, the cleavage rate, blastocyst rate and the cell number of blastocyst (70 +/- 4.5%, 28 +/- 2.4% and 50 +/- 6.5%) were significantly higher (P < 0.05) than that of controls; when only culture medium was supplemented with melatonin, the highest cleavage rate, blastocyst rate and the cell number of blastocyst was observed at 10(-7) m melatonin, which were significantly higher than that of controls (P < 0.05). The best results (cleavage rates 79 +/- 8.4%, blastocyst rates 35 +/- 6.7%) were obtained when both the maturation and culture medium were supplemented with 10(-9) m melatonin respectively (P < 0.05). In conclusion, exogenous melatonin at the proper concentration may improve the in vitro maturation of porcine oocytes and their parthenogenetic embryonic development. Further research is needed to identify the effect of melatonin on in vitro and in vivo oocyte maturation and embryo development in porcine.
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Affiliation(s)
- Jian-Min Shi
- Key Laboratory of Animal Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China
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Gitto E, Pellegrino S, Gitto P, Barberi I, Reiter RJ. Oxidative stress of the newborn in the pre- and postnatal period and the clinical utility of melatonin. J Pineal Res 2009; 46:128-39. [PMID: 19054296 DOI: 10.1111/j.1600-079x.2008.00649.x] [Citation(s) in RCA: 212] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Newborns, and especially those delivered preterm, are probably more prone to oxidative stress than individuals later in life. Also during pregnancy, increased oxygen demand augments the rate of production of reactive oxygen species (ROS) and women, even with normal pregnancies, experience elevated oxidative stress and lipid peroxidation compared with nonpregnant women. Also, there appears to be an increase in ROS generation in the placenta of pre-eclamptic women. In comparison with healthy adults, newborn infants have lower levels of plasma antioxidants such as vitamin E, beta-carotene, and sulphydryl groups, lower levels of plasma metal binding proteins including ceruloplasmin and transferrin, and reduced activity of erythrocyte superoxide dismutase. This review summarizes conditions of newborns where there is elevated oxidative stress. Included in this group of conditions is asphyxia, respiratory distress syndrome and sepsis and the review also summarizes the literature related to clinical trials of antioxidant therapies and of melatonin, a highly effective antioxidant and free radical scavenger. The authors document there is general agreement that short-term melatonin therapy may be highly effective and that it has a remarkably benign safety profile, even when neonates are treated with pharmacological doses. Significant complications with long-term melatonin therapy in children and adults also have not been reported. None of the animal studies of maternal melatonin treatment or in postnatal life have shown any treatment-related side effects. The authors conclude that treatment with melatonin might result in a wide range of health benefits, improved quality of life and reduced healthcare costs and may help reduce complications in the neonatal period.
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Affiliation(s)
- Eloisa Gitto
- Neonatal Intensive Care Unit, Institute of Medical Pediatrics, University of Messina, Messina, Italy
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Kang JT, Koo OJ, Kwon DK, Park HJ, Jang G, Kang SK, Lee BC. Effects of melatonin on in vitro maturation of porcine oocyte and expression of melatonin receptor RNA in cumulus and granulosa cells. J Pineal Res 2009; 46:22-8. [PMID: 18494781 DOI: 10.1111/j.1600-079x.2008.00602.x] [Citation(s) in RCA: 149] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Melatonin is a multifunctional molecule that mediates several circadian and seasonal processes in animal reproduction. Melatonin and its metabolites are antioxidants and free radical scavengers. We investigated the effects of melatonin on porcine oocyte maturation and embryo development. We then investigated the local expression of the melatonin receptor 1 (MT1) gene in cumulus cells, granulosa cells, and the oocytes with the reverse transcription-polymerase chain reaction (RT-PCR) method. We further evaluated the antioxidant effects [reactive oxygen species (ROS) levels in cumulus-oocytes complexes] of melatonin supplementation during in vitro maturation (IVM). Compared with control, melatonin supplementation (10 ng/mL) during IVM resulted in a greater proportion of oocytes extruding the polar body (75.6% versus 84.6%). Significantly greater proportion of parthenogenetically activated oocytes developed to blastocysts when the in vitro medium was supplemented with melatonin; however, cleavage frequency and blastocyst cell number were not affected by the treatment. RT-PCR analysis revealed the expression of MT1 gene in cumulus and granulosa cells but not in oocytes. Melatonin-treated oocytes had significantly lower levels of ROS than did control (untreated) oocytes. We conclude that exogenous melatonin has beneficial effects on nuclear and cytoplasmic maturation during porcine IVM. Some of the observed effects may be mediated by receptor binding and while others may have been receptor independent, e.g., direct free radical scavenging.
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Affiliation(s)
- Jung-Taek Kang
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Korea
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Papis K, Poleszczuk O, Wenta-Muchalska E, Modlinski JA. Melatonin effect on bovine embryo development in vitro in relation to oxygen concentration. J Pineal Res 2007; 43:321-6. [PMID: 17910599 DOI: 10.1111/j.1600-079x.2007.00479.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Melatonin promotes mouse embryo development in vitro. An effect of melatonin on bovine embryo development is described here. Slaughterhouse derived oocytes were subjected to standard in vitro maturation and fertilization procedures. Presumptive zygotes were cultured for 2 days in CR1aaLA medium supplemented with melatonin (10(-4) m) or without melatonin (control). Culture was performed under two different gas atmospheres containing physiological (7%) or atmospheric (20%) oxygen concentrations (2x2 factorial analysis). After day 2, embryos from each treatment group developed to at least four-cell stage, were cultured without melatonin until day 10 at optimum 7% O2 atmosphere. Blastocyst formation rates of presumptive zygotes and of four-cell embryos were calculated for each group. Significant interactions between oxygen tension and the melatonin treatment were found. Out of four-cell embryos put into in vitro culture after initial incubation in medium containing melatonin, decreased blastocyst rate was observed in melatonin group (47.7%) compared with control (67.7%; P=0.0327) when lower oxygen concentration was applied. A beneficial effect of melatonin was observed in 20% O2: out of 61 embryos, 42 (68.9%) developed to the blastocyst stage after treatment in melatonin versus 32 of 63 (50.8%; P=0.0458) blastocysts that developed in control group. In conclusion, beneficial or harmful effects of melatonin on bovine embryo development in vitro were observed, depending on the oxygen tension during the treatment.
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Affiliation(s)
- Krzysztof Papis
- Department of Experimental Embryology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Poland.
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Rodriguez-Osorio N, Kim IJ, Wang H, Kaya A, Memili E. Melatonin increases cleavage rate of porcine preimplantation embryos in vitro. J Pineal Res 2007; 43:283-8. [PMID: 17803526 DOI: 10.1111/j.1600-079x.2007.00475.x] [Citation(s) in RCA: 97] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Melatonin has been used to promote in vitro embryo development in different species. This study determined the effects of melatonin on in vitro porcine embryo development; in particular, cleavage rate, blastocyst rate, and blastocyst cell number. Starting 5 hr after insemination, porcine zygotes were cultured in porcine zygote medium 3 (PZM-3) culture medium supplemented with melatonin at increasing concentrations (10(-12) M, 10(-9) M, 10(-6) M, 10(-3) M). Melatonin at a concentration of 10(-9) M had a positive effect on cleavage rates, while the highest concentration of melatonin (10(-3) M) significantly decreased cleavage rates. Although blastocyst rates were not increased by 10(-9) M melatonin, blastocyst cell numbers were significantly higher for embryos subjected to 10(-9) M melatonin. The expression levels of the pro-apoptotic gene BAX and anti-apoptotic gene BCL2L1 in blastocysts were not affected by the presence of melatonin in the culture medium. To further study the protective properties of 10(-9) M melatonin against stressful conditions, hydrogen peroxide (0.01 mm) and heat (40 degrees C) were used during embryo culture. The addition of melatonin to embryos subjected to 40 degrees C for 3 hr increased cleavage rates, but had no protective effect for embryos subjected to 0.01 mm H(2)O(2), probably because the physiological levels of melatonin could not counteract the pharmacological levels of H(2)O(2). Our data indicate that 10(-9) M melatonin has a positive effect on porcine embryo cleavage rates and blastocyst total cell numbers and it might have a protective effect against heat stress.
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Affiliation(s)
- N Rodriguez-Osorio
- Department of Animal and Dairy Sciences, Mississippi State University, MS 39762, USA
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Abstract
Pineal melatonin regulates circadian rhythms and influences sleep. Melatonin also has protective actions against tissue damage from free-radicals and other toxins. Evidence is presented that this indoleamine is involved in pre- and postnatal brain (and ocular) development and intrauterine growth. In the absence of maternal melatonin, short gestation infants have a prolonged period of melatonin deficiency. Melatonin supplementation, which has a benign safety profile, may help reduce complications in the neonatal period that are associated with short gestation. We believe that this treatment might result in a wide range of health benefits, improved quality of life and reduced healthcare costs.
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Affiliation(s)
- James E Jan
- Melatonin Research Group, Department of Psychiatry, BC Children's Hospital, Vancouver, BC, Canada, and Child Health, Chelsea and Westminster Campus, Imperial College, London, UK.
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Ishizuka B, Kuribayashi Y, Murai K, Amemiya A, Itoh MT. The effect of melatonin on in vitro fertilization and embryo development in mice. J Pineal Res 2000; 28:48-51. [PMID: 10626601 DOI: 10.1034/j.1600-079x.2000.280107.x] [Citation(s) in RCA: 124] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
To examine the effect of melatonin on in vitro fertilization and embryonic development, mouse embryos after insemination in vitro were cultured in a physiological medium with or without melatonin. Melatonin increased the fertilization rate significantly at a concentration between 10(-6) and 10(-4) M (27.6 vs. 43.9 or 40.4%, P < 0.01). Furthermore, a significant increase in the rate of embryos reaching the four-cell stage (16.0 vs. 26.7%, P < 0.01), the eight-cell stage (12.1 vs. 25.8 or 23.5%, P < 0.01), and blastulation (8.9 vs. 23.5 or 17.5%, P < 0.01) was observed when the embryos were cultured in a medium containing 10(-8) or 10(-6) M melatonin. These results demonstrate that melatonin supports fertilization and early embryo development after in vitro fertilization.
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Affiliation(s)
- B Ishizuka
- Department of Obstetrics and Gynecology, University School of Medicine, Kawasaki, Japan.
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Abstract
In a study on the embryotoxicity of pineal indoles on developing chick embryos in vivo, the pineal indoles--namely, melatonin (MEL), methoxytryptamine (MTA) and methoxytryptophol (MTP)--were injected into the yolk sacs of the chick embryos through the air chambers of the eggs on the 4th day of incubation. The eggs were opened and the embryos examined after 6, 10 or 14/15 days of incubation. Abnormalities were found to occur mainly in the 6- and 10-day-old embryos, which exhibited external malformations such as twisted vertebral column, abdominal hernia, exteriorization of heart and viscera, defects of eye, beak and limb. From the results obtained from embryos on the 14th or 15th day of incubation, MEL was found to be the most toxic indole in regard to the mortality induced, whereas MTA had the highest teratogenicity because of the frequent incidence of abnormal embryos. Effect of MTP treatment on the development of chick embryos varied greatly between doses, and there were no abnormal embryos found on the 14th or 15th day of incubation.
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Affiliation(s)
- V E Ooi
- Department of Biology, The Chinese University of Hong Kong, NT, People's Republic of China.
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McElhinny AS, Davis FC, Warner CM. The effect of melatonin on cleavage rate of C57BL/6 and CBA/Ca preimplantation embryos cultured in vitro. J Pineal Res 1996; 21:44-8. [PMID: 8836963 DOI: 10.1111/j.1600-079x.1996.tb00269.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
There is growing interest in using melatonin as a therapeutic agent for the treatment of a variety of medical conditions, including cancer, heart disease, glaucoma, stress, jet lag, and sleep disorders. In addition, melatonin is being evaluated in a clinical trial to test its efficacy as an oral contraceptive. In order to test any possible adverse effects of melatonin on preimplantation embryos, we used the mouse as a model system. Two strains of mice, a Ped fast, melatonin-deficient strain, C57BL/6, and a Ped slow strain previously found to have detectable melatonin levels at nighttime, CBA/Ca, were studied. Two cell embryos were incubated with melatonin concentrations from 10(-5) M to 10(-13) M for 48 or 72 hours and the number of cells per embryo assessed quantitatively at the end of the incubation period. We used sufficiently high levels of melatonin to mimic the pharmacological concentration used in the oral contraceptive. It was found that there was no effect of melatonin on embryos from either mouse strain at any of the concentrations tested. Our results suggest that if conception occurs while melatonin is being administered to treat a range of conditions, it would not adversely affect the embryo.
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Affiliation(s)
- A S McElhinny
- Department of Biology, Northeastern University, Boston, MA 02115, USA
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