| First Author | Sun X | Year | 2018 |
| Journal | Biol Reprod | Volume | 98 |
| Issue | 2 | Pages | 208-217 |
| PubMed ID | 29228105 | Mgi Jnum | J:258275 |
| Mgi Id | MGI:6117646 | Doi | 10.1093/biolre/iox164 |
| Citation | Sun X, et al. (2018) Metformin attenuates susceptibility to inflammation-induced preterm birth in mice with higher endocannabinoid levels. Biol Reprod 98(2):208-217 |
| abstractText | 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. |
