Fig. 2.

Regulation of autophagy by oxidative stress near term. Near term, highly elevated ROS results in induction of 70-kDa heat shock protein (HSPA1A) and transcription factor nuclear factor kappa B (NF-kB). HSPA1A inhibits autophagy through activation of the protein kinase, Akt, that leads to phosphorylation of mammalian target of rapamycin (mTOR), which, in turn, binds to raptor to form the mTORC1 complex that inhibits autophagy. Prolonged NF-kB activation is an additional inhibitor of autophagy through mTORC1 activation. Impaired autophagy leads to intracellular accumulation of abnormal proteins coupled with limited production of the pro-quiescence factors progesterone receptor B (PRB) and caspase 3, thus promoting myometrial contractions. Concomitantly, withdraw of autophagy induces decidual senescence that leads to membrane weakening and production of the senescence-associated secretory phenotype (SASP), further inducing labor