Cardiovascular outcome in 12-month-old male and female offspring of metformin-treated obese mice
Author(s)
Type
Journal Article
Abstract
Metformin is increasingly used to treat diabetes in pregnancy, but the effects on adult offspring health remain under-explored. The present study investigated the long-term cardiovascular effects in male and female offspring of maternal metformin treatment using a well-established mouse model of obese glucose intolerant pregnancy. Female mice were given chow, or an obesogenic diet with/without 300 mg kg−1 day−1 oral metformin during gestation. At 3, 6 and 12 months of age, male and female offspring were studied longitudinally with tail-cuff plethysmography and echocardiography. At 12 months, tissues were collected for wire myography, histology and molecular analyses. Female offspring of obese dams had elevated blood pressure throughout life, cardiac diastolic dysfunction at 3 months, and increased femoral vasoconstrictor reactivity and aortic wall remodelling at 12 months. Metformin treatment did not ameliorate these effects and led to obesity-induced hypertension at 12 months. Irrespective of metformin, male offspring of obese pregnancy had cardiac diastolic dysfunction from 6 months without changes in blood pressure. Male metformin-exposed offspring also showed cardiomegaly, increased cardiac collagen and vascular sympathetic hyperreactivity, suggesting metformin exposure worsened the cardiovascular phenotype. These findings show that maternal obesity caused sex-specific cardiovascular aberrations in aged offspring. Maternal metformin was not corrective and introduced further sex-dependent cardiovascular alterations. Further long-term offspring follow up of both sexes is needed for informed decisions about metformin during pregnancy.
Date Issued
2025-09-01
Date Acceptance
2025-05-24
Citation
Journal of Physiology, 2025, 603 (17), pp.4747-4764
ISSN
0022-3751
Publisher
Wiley
Start Page
4747
End Page
4764
Journal / Book Title
Journal of Physiology
Volume
603
Issue
17
Copyright Statement
© 2025 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40538089
Subjects
BODY-COMPOSITION
cardiac function
DIET-INDUCED OBESITY
DYSFUNCTION
EXPOSURE
gestational diabetes mellitus
hypertension
HYPERTENSION
HYPOXIA
LEADS
Life Sciences & Biomedicine
metformin
Neurosciences
Neurosciences & Neurology
Physiology
PREGNANCY
Science & Technology
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-09-01