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5 December 2017 Metformin attenuates susceptibility to inflammation-induced preterm birth in mice with higher endocannabinoid levels
Xiaofei Sun, Alexandra Tavenier, Wenbo Deng, Emma Leishman, Heather B. Bradshaw, Sudhansu K. Dey
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Abstract

Premature decidual senescence is a contributing factor to preterm birth. Fatty acid amide hydrolase mutant females (Faah/) with higher endocannabinoid levels are also more susceptible to preterm birth upon lipopolysaccharide (LPS) challenge due to enhanced decidual senescence; this is associated with mitogen-activated protein kinase p38 activation. Previous studies have shown that mechanistic target of rapamycin complex 1 (mTORC1) contributes to decidual senescence and promotes the incidence of preterm birth. In this study, we sought to attenuate premature decidual aging in Faah/ females by targeting mTORC1 and p38 signaling pathways. Because metformin is known to inhibit mTOR and p38 signaling pathways, Faah/ females were treated with metformin. These mice had a significantly lower preterm birth incidence with a higher rate of live birth after an LPS challenge on day 16 of pregnancy; metformin treatment did not affect placentation or neonatal birth weight. These results were associated with decreased levels of p38, as well as pS6, a downstream mediator of mTORC1 activity, in day 16 Faah/− decidual tissues. Since metformin treatment attenuates premature decidual senescence with limited side effects during pregnancy, careful use of this drug may be effective in ameliorating specific adverse pregnancy events.

Summary Sentence

Metformin treatment attenuates premature decidual senescence caused by higher endocannabinoid levels and susceptibility to inflammation-induced preterm birth in mice.

© The Author(s) 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Xiaofei Sun, Alexandra Tavenier, Wenbo Deng, Emma Leishman, Heather B. Bradshaw, and Sudhansu K. Dey "Metformin attenuates susceptibility to inflammation-induced preterm birth in mice with higher endocannabinoid levels," Biology of Reproduction 98(2), 208-217, (5 December 2017). https://doi.org/10.1093/biolre/iox164
Received: 8 September 2017; Accepted: 29 November 2017; Published: 5 December 2017
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KEYWORDS
decidual aging
endocannabinoids
FAAH
metformin
preterm birth
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