Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2024; 15(4): 758-768
Published online Apr 15, 2024. doi: 10.4239/wjd.v15.i4.758
Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring
Enriqueta Muñoz-Islas, Edgar David Santiago-SanMartin, Eduardo Mendoza-Sánchez, Héctor Fabián Torres-Rodríguez, Laura Yanneth Ramírez-Quintanilla, Christopher Michael Peters, Juan Miguel Jiménez-Andrade
Enriqueta Muñoz-Islas, Edgar David Santiago-SanMartin, Eduardo Mendoza-Sánchez, Héctor Fabián Torres-Rodríguez, Laura Yanneth Ramírez-Quintanilla, Juan Miguel Jiménez-Andrade, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Reynosa 88740, Tamaulipas, Mexico
Christopher Michael Peters, Department of Anesthesiology, Wake Forest University School of Medicine, Winston Salem, NC 27101, United States
Author contributions: Muñoz-Islas E, Jiménez-Andrade JM, and Peters CM designed and coordinated the study; Muñoz-Islas E contributed to funding acquisition; Santiago-SanMartin ED, Mendoza-Sánchez E, Torres-Rodríguez HF, and Ramírez-Quintanilla LY performed the experiments and acquired and analyzed data; Muñoz-Islas E, Jiménez-Andrade JM, and Peters CM drafted the manuscript; and all authors contributed to the interpretation of the results and critical review of the paper, and approved the final version of the article.
Supported by the National Council for Humanities, Science and Technology of Mexico CONAHCyT, No. CB/2017-2018/A1-S-27869.
Institutional animal care and use committee statement: All animal experiments were conducted following the national guidelines and the relevant national laws on the protection of animals and were approved by the Institutional Research and Ethics Committee of Unidad Académica Multidisciplinaria Reynosa-Aztlán (Approval No. CEI-UAMRA-2021-0003).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available by request (jandrade@docentes.uat.edu.mx). Not additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Juan Miguel Jiménez-Andrade, PhD, Professor, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, 16 Calle y Lago de Chapala, Col. Aztlán, Reynosa 88740, Tamaulipas, Mexico. jandrade@docentes.uat.edu.mx
Received: December 12, 2023
Peer-review started: December 12, 2023
First decision: January 15, 2024
Revised: January 29, 2024
Accepted: March 11, 2024
Article in press: March 11, 2024
Published online: April 15, 2024
Processing time: 121 Days and 3.6 Hours
Abstract
BACKGROUND

Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood, adolescence, and adulthood; however, the mechanisms by which gestational diabetes mellitus (GDM) predisposes offspring to metabolic disorders remain unknown.

AIM

To quantify the nerve axons, macrophages, and vasculature in the pancreas from adult offspring born from mouse dams with GDM.

METHODS

GDM was induced by i.p. administration of streptozotocin (STZ) in ICR mouse dams. At 12 wk old, fasting blood glucose levels were determined in offspring. At 15 wk old, female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry. We quantified the density of sensory [calcitonin gene-related peptide (CGRP)] and tyrosine hydroxylase (TH) axons, blood vessels (endomucin), and macro-phages (CD68) in the splenic pancreas using confocal microscopy.

RESULTS

Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams. However, the density of CGRP+ and TH+ axons, endomucin+ blood vessels, and CD68+ macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring. Likewise, the microvasculature in the islets was significantly greater, but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.

CONCLUSION

GDM induces neuronal, vascular, and inflammatory changes in the pancreas of adult progeny, which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

Keywords: Gestational diabetes mellitus; Immunohistochemistry; Confocal microscopy; Pancreas; Offspring

Core Tip: Gestational diabetes mellitus (GDM) predisposes offspring to develop metabolic disorders later in life, however, the underlying mechanisms are unknown. Here, using a well-established model of GDM, we report that while GDM did not modify body weight or blood glucose, it significantly increased the density of nerve axons, blood vessels, and macrophages in the pancreas of adult offspring born from dams with GDM.