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, ,

  • 1 Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2 Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
  • 3 Department of Obstetrics, The First People's Hospital of Yunnan Province, Kunming, China
  • 4 Liggins Institute, University of Auckland, Auckland, New Zealand
  • 5 College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK
* Co-first authors

Received: March 22, 2020       Accepted: June 4, 2020       Published: July 22, 2020
How to Cite

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.


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.


GDM: gestational diabetes mellitus; T2DM: type 2 diabetes mellitus; HFD: high-fat diet; HPO axis: hypothalamus, pituitary gland, and ovary; GnRH: gonadotropin-releasing hormone; LFD: low-fat diet; OGTT: oral glucose tolerance test; ITT: insulin tolerance test; FSH: follicle-stimulating hormone; GC-MS: gas chromatography-mass spectrometry; PCA: principal component analysis; OPLS-DA: orthogonal partial least squares discriminant analysis; VIP: variable importance projection; AUC: area under the curve.