Figure 1.

A scheme depicting potential contribution of decidual mTORC1 and senescence in setting the parturition clock. Term pregnancy encompasses progressive decidual senescence over the course of pregnancy (pink arrow) until a threshold is encountered, triggering PG synthesis, myometrial activation and contractility, culminating in birth. In the mouse model of preterm labor in which Trp53 is conditionally deleted in the uterus, decidual senescence begins prematurely due to activation of an pAkt-mTORC1-p21-Cox2 signaling axis and reaches the senescence threshold in a shorter gestational time frame, leading to preterm delivery. Several risk factors of preterm birth, including genetics, stress and inflammation/infection have been shown to contribute to the senescence process in other systems, and we speculate that these factors pathologically push decidual senescence toward the threshold. Furthermore, normal parturition involves cervical ripening along with myometrial activation in preparation for parturition, which does not occur in the p53^d/d females: these females exhibit dystocia and stillbirth. Rapamycin, an inhibitor of mTORC1 signaling, can attenuate premature decidual senescence seen in p53^d/d females and rescue preterm labor (Adapted from ¹¹⁰).