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Research Paper|Volume 12, Issue 14|pp 14019—14036

Metformin administration during pregnancy attenuated the long-term maternal metabolic and cognitive impairments in a mouse model of gestational diabetes

Yalan Zhao1,2,3, Xiaobo Zhou1, Xue Zhao1, Xinyang Yu1, Andi Wang1, Xuyang Chen1, Hongbo Qi1, Ting-Li Han1,2,4, Hua Zhang1,2, Philip N. Baker5
  • 1Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
  • 3Department of Obstetrics, The First People's Hospital of Yunnan Province, Kunming, China
  • 4Liggins Institute, University of Auckland, Auckland, New Zealand
  • 5College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK
* Co-first authors
Received: March 22, 2020Accepted: June 4, 2020Published: July 22, 2020
https://doi.org/10.18632/aging.103505

Copyright: © 2020 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Gestational diabetes mellitus (GDM) is a metabolic disease that can have long-term adverse effects on the cognitive function of mothers. In our study, we explored the changes in metabolic health and cognitive function in mice of middle- and old- age after exposure to GDM, and whether metformin therapy during pregnancy provided long-term benefits.

Results: Mice with GDM demonstrated significant cognitive impairment in old age, which was associated with insulin resistance. Gestational metformin therapy was shown to increase insulin sensitivity and improve cognition. The ovarian aging rate was also accelerated in mice exposed to GDM during pregnancy, which may be related to fatty acid metabolism in the ovaries.

Conclusion: Treatment with metformin during pregnancy was shown to improve fatty acid metabolism in ovarian tissues.

Method: During pregnancy, mice were fed with a high-fat diet (GDM group) or a low-fat diet (Control group), and a third group received metformin while receiving a high-fat diet (Treatment group). At 12 months old, the mice completed an oral glucose tolerance test, insulin tolerance test, Morris water maze test, female sex hormones were measured, and metabolite profiles of tissue from the ovaries, hypothalamus, and pituitary glands were analysed using gas chromatography-mass spectrometry.