Yao Xiaohong, Wang Chaofan, Yu Weiran, Sun Longjie, Lv Zheng, Xie Xiaomei, Tian Shuang, Yan Lu, Li Lei, Liu Jiali
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
FASEB J. 2024 Jan;38(1):e23361. doi: 10.1096/fj.202301234RR.
Oocyte meiotic prophase I (MI) is an important event in female reproduction. Breast cancer amplified sequence 2 (BCAS2) is a component of the spliceosome. Previous reports have shown that BCAS2 is critical in male germ cell meiosis, oocyte development, and early embryo genome integrity. However, the role of BCAS2 in oocyte meiosis has not been reported. We used Stra8-GFPCre mice to knock out Bcas2 in oocytes during the pachytene phase. The results of fertility tests showed that Bcas2 conditional knockout (cKO) in oocytes results in infertility in female mice. Morphological analysis showed that the number of primordial follicles in the ovaries of 2-month-old (M) mice was significantly reduced and that follicle development was blocked. Further analysis showed that the number of primordial follicles decreased and that follicle development was slowed in 7-day postpartum (dpp) ovaries. Moreover, primordial follicles undergo apoptosis, and DNA damage cannot be repaired in primary follicle oocytes. Meiosis was abnormal; some oocytes could not reach the diplotene stage, and more oocytes could not develop to the dictyotene stage. Alternative splicing (AS) analysis revealed abnormal AS of deleted in azoospermia like (Dazl) and diaphanous related formin 2 (Diaph2) oogenesis-related genes in cKO mouse ovaries, and the process of AS was involved by CDC5L and PRP19.
卵母细胞减数分裂前期I（MI）是雌性生殖中的一个重要事件。乳腺癌扩增序列2（BCAS2）是剪接体的一个组成部分。先前的报道表明，BCAS2在雄性生殖细胞减数分裂、卵母细胞发育和早期胚胎基因组完整性方面至关重要。然而，BCAS2在卵母细胞减数分裂中的作用尚未见报道。我们使用Stra8-GFPCre小鼠在粗线期敲除卵母细胞中的Bcas2。生育力测试结果表明，卵母细胞中Bcas2条件性敲除（cKO）导致雌性小鼠不育。形态学分析显示，2月龄（M）小鼠卵巢中的原始卵泡数量显著减少，卵泡发育受阻。进一步分析表明，产后7天（dpp）卵巢中的原始卵泡数量减少，卵泡发育减缓。此外，原始卵泡发生凋亡，初级卵泡卵母细胞中的DNA损伤无法修复。减数分裂异常；一些卵母细胞无法达到双线期，更多的卵母细胞无法发育到核网期。可变剪接（AS）分析揭示了cKO小鼠卵巢中无精子症样缺失（Dazl）和透明相关成膜蛋白2（Diaph2）等卵子发生相关基因的AS异常，且AS过程受CDC5L和PRP19影响。
