卵母细胞特异性蛋白 OMC1 在完整生殖寿命中维持染色体黏连
Oocyte-specific OMC1 is required for maintaining chromosome cohesion through reproductive life
摘要
哺乳动物卵母细胞在胎儿期进入减数分裂后长期停滞,由不可更新的 REC8 黏连蛋白介导的染色体黏连随年龄逐渐退化,导致成年减数分裂恢复时出现染色体分离错误。该研究鉴定出卵母细胞特异性染色体蛋白 OMC1,其从胎儿期至成年成熟期始终定位于含 REC8-黏连蛋白的染色体轴;利用 Omc1 敲除小鼠证明,OMC1 是维持黏连蛋白直至减数分裂成熟完成所必需,可抑制年龄相关的染色体分离异常。研究揭示了雌性生殖细胞内在的、支持生殖寿命并抑制卵子非整倍体的分子基础。
原文摘要
In mammals, oocytes initiate meiosis during fetal development and then enter a prolonged meiotic arrest. During this female-specific long-term arrest, chromosome cohesion mediated by nonrenewable REC8 cohesin gradually deteriorates, predisposing oocytes to age-associated chromosome segregation errors when meiosis resumes for maturation in adulthood. Female-specific factors that counteract this deterioration remain unknown. Here we identify OMC1 as an oocyte-specific chromosomal protein required for the maintenance of chromosome cohesion through reproductive life. OMC1 associates with REC8-cohesin-containing chromosome axes from fetal stages through adult meiotic maturation. Using Omc1 knockout mice, we show that OMC1 is required for cohesin maintenance until completion of meiotic maturation, thereby suppressing age-associated chromosome segregation errors. These findings provide insight into the female germ-cell-intrinsic molecular basis that supports reproductive longevity by suppressing age-associated chromosome cohesion loss, which leads to egg aneuploidy, a major cause of infertility and congenital disorders.
推荐理由:首次报道卵母细胞特异性因子 OMC1 作为对抗黏连蛋白随龄退化的关键分子,直接关联卵子非整倍体与女性生育力衰退这一核心问题;机制清晰、有敲除小鼠体内验证,对卵母细胞老化研究有明确推进价值。
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