PIEZO1-mediated endometrial decidualization is disrupted in miscarriage through BECN1-dependent autophagy

Le résumé fourni par la source

Miscarriage is a major challenge in reproductive medicine, with impaired decidualization as a key contributing factor. The mechanosensitive ion channel PIEZO1 responds to mechanical forces including shear stress, stretch, and extracellular matrix (ECM) stiffness. Here, we report that PIEZO1 is decreased in decidua from miscarriage patients and show it plays a crucial role in decidualization in response to ECM stiffness and cell contraction. Uterine-specific Piezo1 knockout (Pgr-Cre) causes subfertility due to decidualization impairment in mid-late pregnancy, and PIEZO1 silencing in human endometrial stromal cells similarly impairs decidualization. The PIEZO1 agonist Yoda1 enhances decidualization in both in vivo and in vitro models. Optimal decidualization occurs on 25 kPa ECM substrates and is abolished by Piezo1 deletion. Mechanistically, PIEZO1 regulates decidualization via Ca²⁺-CaMKII signaling and BECN1-dependent autophagy: blocking Ca²⁺ or pCaMKII inhibits Yoda1-enhanced decidualization, Beclin1 silencing abolishes it, and Tat-BECN1 fully rescues decidualization failure caused by PIEZO1 deficiency. Finally, PIEZO1 expression is reduced in endometrium from endometriotic baboons, consistent with impaired decidualization. These findings uncover a PIEZO1-mediated mechanotransduction mechanism regulating decidualization with implications for miscarriage and endometriosis. PIEZO1, a mechanosensitive ion channel, promotes endometrial decidualization via Ca²⁺ CaMKII-BECN1 autophagy. Its deficiency impairs decidualization in mice and humans, linking mechanical signals to miscarriage.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.