Department of Obstetrics and Gynecology, Anqing Municipal Hospital, Anqing Medical Center of Anhui Medical University, Anqing, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
Mol Cell Endocrinol. 2024 Jan 15;580:112090. doi: 10.1016/j.mce.2023.112090. Epub 2023 Oct 25.
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.
蜕膜化是妊娠早期胚胎植入所必需的过程。蜕膜化缺陷是早期妊娠丢失（EPL）的一个关键主要原因。泛素特异性蛋白酶 7（USP7）是一种参与子宫功能的去泛素化酶。本研究旨在探讨 USP7 调节 EPL 中蜕膜化的潜在机制。我们发现，EPL 患者的蜕膜组织中 USP7 下调。USP7 的上调增强了子宫内膜基质细胞（ESCs）的蜕膜化，增加了蜕膜化生物标志物 IGFBP1 和 PRL 以及孕激素受体 A/B（PR-A/B）的表达。此外，我们发现信号转导和转录激活因子 3（STAT3）是 ESCs 中 USP7 的直接靶标。USP7 通过去泛素化与 STAT3 结合，并增加 ESCs 中的 STAT3 水平。抑制 STAT3 阻碍了 USP7 促进的 ESCs 活力、蜕膜化和 PR-A/B 表达。USP7 通过 STAT3/PR 信号通路促进 ESCs 的蜕膜化，这为 EPL 的病理机制提供了新的见解，并可能有助于 EPL 的临床治疗。
