Galectin-1 Signaling Dysregulation Impairs Stromal Senescence and Decidualization in Recurrent Implantation Failure.

Abstract

Endometrial decidualization is indispensable for embryo implantation, and moderate cellular senescence has recently been recognized as a functional component of this process. However, how this senescence response is regulated upstream and whether its disruption contributes to recurrent implantation failure (RIF) remain unclear. Here, we identify Galectin-1 (GAL1) as a potential regulator of senescence-associated decidual responses in human endometrial stromal cells. Moderate senescence induction in human endometrial stromal cells and primary decidual stromal cells (DSCs) was accompanied by enhanced decidualization responses, which was further supported by the co-localization of senescence markers with bone morphogenetic protein 2 (Bmp2) in the murine decidual zone during early gestation. GAL1 promoted senescence-associated and decidualization responses, whereas GAL1 inhibition or LGALS1 knockdown attenuated these effects. Estradiol and progesterone treatment increased GAL1 secretion and the expression of GAL1-associated extracellular components, while integrin inhibition reduced GAL1-induced decidual responses. In RIF endometrium, GAL1 expression was elevated, whereas genes associated with GAL1 signaling were downregulated in stromal cells, accompanied by reduced senescence marker expression. Collectively, our findings identify GAL1 signaling dysregulation as a potential mechanism underlying insufficient stromal senescence and impaired decidualization in a subset of RIF endometrium, providing new insights into the molecular heterogeneity of RIF.