Wang Yibo, Wang Wenji, Cheng Kaixin, Geng Kaiying, Liang Jing, Wang Peike, Zhang Jiawei, Niu Shudong, Jia Longzhong, Zhang Shuo, Li Lingyu, Feng Xiean, Wang Chao, Wang Haibin, Zhang Hua, Zhang Yan
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
School of Life Science, Taizhou University, Taizhou, China.
Front Cell Dev Biol. 2022 Nov 3;10:1010601. doi: 10.3389/fcell.2022.1010601. eCollection 2022.
Ovarian follicles are the fundamental structure to support oocyte development, which provides mature oocytes for offspring. This process requires granulosa cells (GCs) to respond to the midcycle surge of hormones, leading to GC proliferation and differentiation by a series of genes' transcriptional expression changes. Epigenetic mediator, Polycomb Repressive Complex 1 (PRC1) has been reported to function in fetal ovarian development. However, its functional relevance to folliculogenesis and ovulation remains unknown. In this study, we demonstrated that GC-selective depletion of PCGF2, a key component of PRC1, led to the loss of follicles, ovulation defects, and a lengthened estrus cycle, resulting in subfertility in female mice. The expression of PCGF2 is in the GCs of growing follicles and increases after human chorionic gonadotropin (hCG) stimulation. PCGF2 bound to the promoter of the key ovulation gene progesterone receptor () and upregulated the expression of by targeting the epigenetic modification of H2AK119ub1 after hCG surge. Consistently, the expression of downstream genes of also sharply decreased, which resulted in the follicular rupture failed and oocyte entrapped in corpus luteum in GC-specific knockout mice. Together, our study identified that PCGF2 is essential for folliculogenesis and ovulation modulating hormone receptor expression.
卵巢卵泡是支持卵母细胞发育的基本结构，为后代提供成熟卵母细胞。这一过程需要颗粒细胞（GCs）对激素的中期激增作出反应，通过一系列基因的转录表达变化导致GCs增殖和分化。据报道，表观遗传介质多梳抑制复合体1（PRC1）在胎儿卵巢发育中发挥作用。然而，其与卵泡发生和排卵的功能相关性仍不清楚。在本研究中，我们证明，PRC1的关键成分PCGF2在GCs中的选择性缺失导致卵泡丢失、排卵缺陷和发情周期延长，导致雌性小鼠生育力下降。PCGF2的表达存在于生长卵泡的GCs中，在人绒毛膜促性腺激素（hCG）刺激后增加。hCG激增后，PCGF2与关键排卵基因孕激素受体（）的启动子结合，并通过靶向H2AK119ub1的表观遗传修饰上调的表达。一致地，的下游基因表达也急剧下降，这导致GC特异性敲除小鼠的卵泡破裂失败，卵母细胞被困在黄体中。总之，我们的研究确定PCGF2对卵泡发生和排卵调节激素受体表达至关重要。
