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Hufnagel, A, Fernandez‐Twinn, DS, Blackmore, HL, Ashmore, TJ, Heaton, RA, Jenkins, B, Koulman, A, Hargreaves, IP, Aiken, CE and Ozanne, SE (2021) Maternal but not fetoplacental health can be improved by metformin in a murine diet‐induced model of maternal obesity and glucose intolerance. The Journal of Physiology. ISSN 0022-3751
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Maternal but not fetoplacental health can be improved by metformin in a murine diet-induced model of maternal obesity and glucose intolerance.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Maternal obesity is a global problem that increases the risk of short- and long-term adverse outcomes for mother and child, many of which are linked to gestational diabetes mellitus. Effective treatments are essential to prevent the transmission of poor metabolic health from mother to child. Metformin is an effective glucose lowering drug commonly used to treat gestational diabetes mellitus; however, its wider effects on maternal and fetal health are poorly explored. In this study we used a mouse (C57Bl6/J) model of diet-induced (high sugar/high fat) maternal obesity to explore the impact of metformin on maternal and feto-placental health. Metformin (300 mg/kg/day) was given to obese females via the diet and was shown to achieve clinically relevant concentrations in maternal serum (1669±568 nM in late pregnancy). Obese dams developed glucose intolerance during pregnancy and had reduced uterine artery compliance. Metformin treatment of obese dams improved maternal glucose tolerance, reduced maternal fat mass, and restored uterine artery function. Placental efficiency was reduced in obese dams, with increased calcification and reduced labyrinthine area. Consequently, fetuses from obese dams weighed less (p<0.001) at the end of gestation. Despite normalisation of maternal parameters, metformin did not correct placental structure or fetal growth restriction. Metformin levels were substantial in the placenta and fetal circulation (109.7±125.4 nmol/g in the placenta and 2063±2327 nM in fetal plasma). These findings reveal the distinct effects of metformin administration during pregnancy on mother and fetus and highlight the complex balance of risk versus benefits that are weighed in obstetric medical treatments.
| Item Type: | Article |
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| Additional Information: | This is the peer reviewed version of the following article: Hufnagel, A., Fernandez-Twinn, D.S., Blackmore, H.L., Ashmore, T.J., Heaton, R.A., Jenkins, B., Koulman, A., Hargreaves, I.P., Aiken, C.E. and Ozanne, S.E. (2021), Maternal but not fetoplacental health can be improved by metformin in a murine diet-induced model of maternal obesity and glucose intolerance. J Physiol., which has been published in final form at https://doi.org/10.1113/JP281902 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions |
| Uncontrolled Keywords: | 06 Biological Sciences, 11 Medical and Health Sciences |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RG Gynecology and obstetrics R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Wiley |
| Date Deposited: | 13 Sep 2021 11:17 |
| Last Modified: | 29 Sep 2022 00:50 |
| DOI or ID number: | 10.1113/jp281902 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/15479 |
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