Han Shan, Xie Yanqiu, Lv Jiale, Sun Xuedong, Shi Yuhua
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Reproductive Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Front Cell Dev Biol. 2025 May 19;13:1607161. doi: 10.3389/fcell.2025.1607161. eCollection 2025.
The endocrine functions exerted by ovarian granulosa cells (GCs) are crucial factors in maintaining follicle development, as oocyte development relies on providing energy substrates and cytokines by ovarian granulosa cells. The mRNA deadenylase level of granulosa cells precisely regulates the follicular development processes. In this study, we detect the expression level of the deadenylase CNOT6L in polycystic ovarian syndrome (PCOS) patients' granulosa cells and mouse models' ovaries. The results found that the CNOT6L significantly upregulated in the ovarian granulosa cells of both PCOS patients and mouse models. Subsequently, we conducted the overexpressed granulosa cells to explore the alterations by which CNOT6L regulates ovarian granulosa cell function. The overexpression of CNOT6L in granulosa cells significantly inhibited the glycolytic pathway, activated the mitochondrial oxidative phosphorylation pathway, led to a reduction in the generation of the intermediate product lactate, and resulted in impaired energy supply to the oocyte. Subsequently, we performed Full-length transcriptome sequencing on the granulosa cells and investigated the impact of mRNA poly(A) level differences on granulosa cell dysfunction in PCOS. This study offers new insights into the role of CNOT6L in regulating energy metabolism homeostasis and its involvement in follicular developmental disorders related to polycystic ovary syndrome.
卵巢颗粒细胞（GCs）发挥的内分泌功能是维持卵泡发育的关键因素，因为卵母细胞的发育依赖于卵巢颗粒细胞提供能量底物和细胞因子。颗粒细胞的mRNA去腺苷酸化酶水平精确调节卵泡发育过程。在本研究中，我们检测了多囊卵巢综合征（PCOS）患者颗粒细胞和小鼠模型卵巢中去腺苷酸化酶CNOT6L的表达水平。结果发现，PCOS患者和小鼠模型的卵巢颗粒细胞中CNOT6L均显著上调。随后，我们对颗粒细胞进行过表达，以探究CNOT6L调节卵巢颗粒细胞功能的变化。颗粒细胞中CNOT6L的过表达显著抑制糖酵解途径，激活线粒体氧化磷酸化途径，导致中间产物乳酸生成减少，并导致向卵母细胞的能量供应受损。随后，我们对颗粒细胞进行全长转录组测序，并研究mRNA poly(A)水平差异对PCOS颗粒细胞功能障碍的影响。本研究为CNOT6L在调节能量代谢稳态中的作用及其参与多囊卵巢综合征相关卵泡发育障碍提供了新的见解。
