Myometrial mechanotransduction and the timing of parturition: ion-channel pathways linking uterine stretch, calcium signaling, and inflammation.

Mechanical loading is a defining feature of pregnancy, yet its integration with ion-channel physiology in the myometrium remains incompletely synthesized. This Review examines how uterine stretch, overdistension, oxytocin-associated signaling, extracellular-matrix context, and inflammatory cues are translated into Ca²+ entry, membrane excitability, inflammatory amplification, and contraction timing in the pregnant myometrium. It distinguishes candidate direct mechanosensors from mechanically regulated Ca²+/inflammatory coupling pathways and from adjacent excitability regulators, with the strongest human myometrial evidence currently centered on PIEZO1 and setting-limited TRPV4 signaling. It further separates physiologic term parturition from overdistension-associated premature activation and infection/inflammation-associated preterm birth, which can share downstream modules without being mechanistically interchangeable. Finally, it defines the experimental and translational boundaries that remain to be resolved before channel-centered mechanisms can be interpreted as pharmacologic or clinical intervention strategies.