Down-regulation of S100P induces apoptosis in endometrial epithelial cell during GnRH antagonist protocol

作者：Dan Zhang, Mi Han, Mingjuan Zhou, Mengyu Liu, Yan Li, Bufang Xu, Aijun Zhang · 发表于：Reproductive Biology and Endocrinology · 年份：2021 · DOI：10.1186/s12958-021-00787-0 · 被引用次数：20 · 研究领域：Reproductive System and Pregnancy、S100 Proteins and Annexins、Preterm Birth and Chorioamnionitis

BACKGROUND: The gonadotropin-releasing hormone (GnRH) antagonist protocol for in vitro fertilization (IVF) often leads to lower pregnancy rates compared to the GnRH agonist protocol. Decreased endometrial receptivity is one reason for the lower success rate, but the mechanisms underlying this phenomenon remain poorly understood. The S100 calcium protein P (S100P) is a biomarker for endometrial receptivity. Both GnRH antagonist and S100P are involved in mediating cell apoptosis. However, the involvement of S100P in reduced endometrial receptivity during the GnRH antagonist protocol remains unclear. METHODS: Endometrial tissue was collected at the time of implantation window from patients undergoing the GnRH agonist (GnRH-a) or GnRH antagonist (GnRH-ant) protocols, as well as from patients on their natural cycles. Endometrial cell apoptosis and expression levels of S100P, HOXA10, Bax, and Bcl-2 were assessed. Ishikawa cells were cultured to evaluate the effects that GnRH antagonist exposure or S100P up- or down- regulation had on apoptosis. RESULTS: Endometrial tissue from patients in the GnRH-ant group showed elevated apoptosis and decreased expression of the anti-apoptotic marker Bcl-2. In addition, endometrial expression of S100P was significantly reduced in the GnRH-ant group, and expression of HOXA10 was lower. Immunofluorescence colocalization analysis revealed that S100P was mainly distributed in the epithelium. In vitro experiments showed that knockdown of S100P in Ishi...