Xie Yating, Guo Wenya, Shen Xi, Yu Weina, Kuang Yanping, Chen Qiuju, Long Hui, Lyu Qifeng, Wang Li
Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China.
iScience. 2023 Jul 8;26(8):107357. doi: 10.1016/j.isci.2023.107357. eCollection 2023 Aug 18.
Progestin-primed ovarian stimulation (PPOS) is a new ovulation stimulation protocol, and its role in ovulation and regulatory mechanism is unclear. The clinical PPOS protocol was simulated in mice. The ovulated oocytes, estradiol, progesterone, and luteinizing hormone (LH) levels were analyzed at different hours after trigger. mRNA extraction and real-time PCR, hematoxylin and eosin staining, and immunofluorescence of ovaries were used to explore the involved signaling pathways. The PPOS group had a delayed ovulation at 12.5 h after trigger. Its suppressed LH level reduced the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) on the preovulatory follicles before trigger and significantly decreased the following progesterone synthesis, blood progesterone level, and progesterone receptor (PGR) expression within 4-6 h after trigger. Furthermore, the important ovulatory genes regulated by PGR including ADAMTS-1, VEGF-A, and EDN2 were downregulated, ultimately delaying the ovulation. PPOS suppresses the LH level before trigger and decreases the synthesis of progesterone after trigger, thus delaying the ovulation by downregulating the LHCGR-PGR pathway.
孕激素预处理的卵巢刺激（PPOS）是一种新的排卵刺激方案，其在排卵中的作用及调节机制尚不清楚。在小鼠中模拟了临床PPOS方案。在触发后的不同时间点分析排卵的卵母细胞、雌二醇、孕酮和促黄体生成素（LH）水平。采用mRNA提取和实时PCR、苏木精-伊红染色以及卵巢免疫荧光来探索相关信号通路。PPOS组在触发后12.5小时排卵延迟。其LH水平受到抑制，降低了触发前排卵前卵泡上促黄体生成素/绒毛膜促性腺激素受体（LHCGR）的表达，并在触发后4 - 6小时内显著降低了随后的孕酮合成、血孕酮水平和孕酮受体（PGR）表达。此外，由PGR调节的重要排卵基因包括ADAMTS - 1、VEGF - A和EDN2均下调，最终导致排卵延迟。PPOS在触发前抑制LH水平，触发后降低孕酮合成，从而通过下调LHCGR - PGR途径延迟排卵。
