Primary oocytes with cellular senescence features are involved in ovarian aging in mice.
Primary oocytes with cellular senescence features are involved in ovarian aging in mice.
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具有细胞衰老特征的原代卵母细胞参与小鼠卵巢衰老。
DOI：
10.1101/2024.01.08.574768
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Lei,Lei
中科院分区：
文献类型：
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作者：
Yan,Hao;Miranda,EdgarAndresDiaz;Jin,Shiying;Wilson,Faith;An,Kang;Godbee,Brooke;Zheng,Xiaobin;Brau-Rodríguez,AstridRoshealy;Lei,Lei
在哺乳动物雌性中，静止的原始卵泡作为卵巢储备并通过卵泡发生维持正常的卵巢功能和卵子产生。原始卵泡的丧失导致卵巢衰老。细胞衰老，其特征在于细胞周期停滞和衰老相关分泌表型（SASP）的产生，与组织衰老有关。在本研究中，我们报告了一些静止的初级卵母细胞的原始卵泡成为衰老的成年小鼠卵巢。衰老的初级卵母细胞具有衰老体细胞的衰老标记。在年轻成年小鼠卵巢中观察到衰老的初级卵母细胞，在6 - 12个月的卵巢老化过程中，衰老的初级卵母细胞约占总初级卵母细胞的15%，并在老化的卵巢中积累。给3个月大的小鼠施用衰老药物ABT 263降低了衰老的初级卵母细胞的百分比和卵巢中SASP因子的转录，此外，导致原始卵泡和总卵泡的数量增加以及卵母细胞成熟率更高。我们的研究提供了实验证据表明，初级卵母细胞，一种生殖细胞类型，在减数分裂中被逮捕，成为衰老的成年小鼠卵巢和衰老细胞清除减少原始卵泡损失和减轻卵巢衰老表型。
In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP factors in the ovary, in addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.