Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, 150081, China.
Public Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.
Cell Death Dis. 2021 Dec 20;13(1):21. doi: 10.1038/s41419-021-04374-4.
Premature ovarian insufficiency (POI) is a heterogeneous and multifactorial disorder. In recent years, there has been an increasing interest in research on the pathogenesis and treatment of POI, owing to the implementation of the second-child policy in China. Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is an RNA-binding protein that can bind to specific RNA sequences. CPEB3 can bind to and affect the expression, cellular location, and stability of target RNAs. Cpeb3 is highly expressed in the ovary; however, its functions remain unknown. In this study, Cpeb3-mutant mice were used to characterize the physiological functions of CPEB3. Cpeb3-mutant female mice manifested signs of gradual loss of ovarian follicles, ovarian follicle development arrest, increased follicle atresia, and subfertility with a phenotype analogous to POI in women. Further analysis showed that granulosa cell proliferation was inhibited and apoptosis was markedly increased in Cpeb3-mutant ovaries. In addition, the expression of Gdf9, a potential target of CPEB3, was decreased in Cpeb3-mutant ovaries and oocytes. Altogether, these results reveal that CPEB3 is essential for ovarian follicle development and female fertility as it regulates the expression of Gdf9 in oocytes, disruption of which leads to impaired ovarian follicle development and POI.
卵巢早衰（POI）是一种异质性和多因素疾病。近年来，由于中国实施了二胎政策，人们对 POI 的发病机制和治疗方法的研究产生了越来越大的兴趣。细胞质多聚腺苷酸化元件结合蛋白 3（CPEB3）是一种 RNA 结合蛋白，能够与特定的 RNA 序列结合。CPEB3 可以结合并影响靶 RNA 的表达、细胞定位和稳定性。Cpeb3 在卵巢中高表达；然而，其功能尚不清楚。在这项研究中，使用 Cpeb3 突变小鼠来表征 CPEB3 的生理功能。Cpeb3 突变雌性小鼠表现出卵巢卵泡逐渐丧失、卵泡发育停滞、卵泡闭锁增加和生育力下降的迹象，其表型类似于女性的 POI。进一步分析表明，Cpeb3 突变卵巢中的颗粒细胞增殖受到抑制，细胞凋亡明显增加。此外，Cpeb3 突变卵巢和卵母细胞中 Gdf9 的表达减少，Gdf9 是 CPEB3 的一个潜在靶标。总之，这些结果表明，CPEB3 对于卵泡发育和女性生育力至关重要，因为它调节卵母细胞中 Gdf9 的表达，其破坏导致卵巢卵泡发育受损和 POI。
