Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250001, China.
The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, Shandong 250001, China.
Sci Adv. 2019 Aug 14;5(8):eaax1101. doi: 10.1126/sciadv.aax1101. eCollection 2019 Aug.
Meiosis is a specialized type of cell division that creates haploid germ cells and ensures their genetic diversity through homologous recombination. We show that the H3K4me3 reader ZCWPW1 is specifically required for meiosis prophase I progression in male but not in female germ cells in mice. Loss of in male mice caused a complete failure of synapsis, resulting in meiotic arrest at the zygotene to pachytene stage, accompanied by incomplete DNA double-strand break repair and lack of crossover formation, leading to male infertility. In oocytes, deletion of only somewhat slowed down meiosis prophase I progression; oocytes were able to complete meiosis, and female mice had normal fertility until mid-adulthood. We conclude that the H3K4me3 reader ZCWPW1 is indispensable for meiosis synapsis in males but is dispensable for females. Our results suggest that ZCWPW1 may represent a previously unknown, sex-dependent epigenetic regulator of germ cell meiosis in mammals.
减数分裂是一种特殊的细胞分裂类型，它产生单倍体生殖细胞，并通过同源重组确保其遗传多样性。我们发现，H3K4me3 阅读器 ZCWPW1 特异性地需要在雄性生殖细胞中而不是在雌性生殖细胞中推进减数分裂前期 I 进程。在雄性小鼠中缺失 会导致联会完全失败，导致减数分裂停滞在粗线期到双线期，伴随着不完全的 DNA 双链断裂修复和缺乏交叉形成，导致雄性不育。在卵母细胞中，缺失 只是稍微减缓了减数分裂前期 I 的进程； 卵母细胞能够完成减数分裂，并且 雌性小鼠在成年中期之前具有正常的生育能力。我们得出结论，H3K4me3 阅读器 ZCWPW1 对于雄性生殖细胞的联会是必不可少的，但对于雌性是可有可无的。我们的结果表明，ZCWPW1 可能代表了一种以前未知的、依赖于性别的哺乳动物生殖细胞减数分裂的表观遗传调节剂。
