Progesterone receptor isoform B regulates theOxtr-Plcl2-Trpc3pathway to suppress uterine contractility

Significance Preterm birth affects 10 to 12% of all pregnancies and is the primary cause of neonatal morbidity and mortality worldwide, while prolonged labor increases the risks of infection, uterine rupture, and neonatal distress. Progesterone suppresses uterine contractions. As humans maintain high levels of progesterone throughout parturition, a “functional progesterone withdrawal” hypothesis suggests that switching between myometrial PGR-A and PGR-B isoform activities is crucial for transitioning into the parturition mode. Our mouse models provide evidence in support of this hypothesis. These findings also demonstrate a significant difference in downstream transcriptomic landscapes between the two PGR isoforms. Therefore, this work opens a venue to investigate the PGR isoform interacting signaling for parturition control, providing a possible pathway for developing clinical therapies.