USP7 promotes decidualization of ESCs by STAT3/PR axis during early pregnancy

Decidualization is an essential process for embryo implantation during early pregnancy. Defective decidualization is a critical leading cause of early pregnancy loss (EPL). Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that is involved in uterine function. This study aimed to explore the underlying mechanism by which USP7 regulates decidualization in EPL. We found that USP7 was downregulated in the decidual tissue of EPL patients. Upregulation of USP7 enhanced decidualization in endometrial stromal cells (ESCs), with increased decidualized biomarkers IGFBP1 and PRL and progesterone receptor A/B (PR-A/B) expression. Moreover, we found that signal transducer and activator of transcription 3 (STAT3) is a direct target of USP7 in ESCs. USP7 bound to STAT3 by deubiquitination and increased STAT3 levels in ESCs. Suppression of STAT3 impeded the USP7-promoted cell viability, decidualization, and PR-A/B expression of ESCs. USP7 promoted the decidualization of ESCs through the STAT3/PR signaling pathway during early pregnancy, which provides new insight into the pathological mechanism of EPL and may contribute to the clinical treatment of EPL.