Endometrial Stromal Cell Senescence: A Non‐Negligible Factor in Recurrent Pregnancy Loss

ABSTRACT Recurrent pregnancy loss (RPL) affects approximately 1%–2% of couples of reproductive age, imposing a substantial physiological and psychological burden on patients. Concurrently, against the backdrop of global population aging, the association between female reproductive aging and infertility is increasingly evident. Cellular senescence is typically characterized by an essentially irreversible cell‐cycle arrest and widespread cellular injury, culminating in tissue dysfunction. Aberrant senescence of endometrial stromal cells (EnSCs) may contribute to RPL by compromising endometrial receptivity and impeding embryo implantation and subsequent development, among other mechanisms. However, the interplay between cellular senescence and tissue or organismal function is complex and interdependent. In the endometrium, senescence of EnSCs engages in bidirectional crosstalk with the tissue‐specific process of decidualization. Based on existing literature, this article aims to: (1) elucidate how cellular aging is both a component of normal decidualization and may be involved in the progression of RPL; (2) speculate on the cellular event sequence involved in EnSCs aging during normal and damaged decidualization processes. In‐depth analysis of the interaction between EnSCs aging and decidualization will help propose targeted anti‐aging therapies to eliminate aging cells, as a potential strategy for restoring damaged endometrial receptivity and improving the success rate of in vitro fertilization.