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Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation

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单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Reprod Med Ctr, 1095 Jiefang Rd, Wuhan 430030, Peoples R China
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关键词: In vitro maturation Rapamycin mTOR Oocyte quality DNA damage

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Background Increasing evidence has shown that the mammalian target of rapamycin (mTOR) pathway plays a critical role in oocyte meiosis and embryonic development, however, previous studies reporting the effects of rapamycin on oocyte IVM showed different or even opposite results, and the specific mechanisms were not clear. Methods The immature oocytes from female mice underwent IVM with rapamycin at different concentrations to select an optimal dose. The maturation rate, activation rate, subsequent cleavage and blastocyst formation rates, spindle assembly, chromosome alignment, mitochondrial membrane potential (MMP), ROS levels, and DNA damage levels were evaluated and compared in oocytes matured with or without rapamycin. In addition, the expression levels of genes associated with mTORC1 pathway, spindle assembly, antioxidant function, and DNA damage repair (DDR) were also assessed and compared. Results Rapamycin at 10 nM was selected as an optimal concentration based on the higher maturation and activation rate of IVM oocytes. Following subsequent culture, cleavage and blastocyst formation rates were elevated in activated embryos from the rapamycin group. Additionally, oocytes cultured with 10 nM rapamycin presented decreased ROS levels, reduced chromosome aberration, and attenuated levels of gamma-H2AX. No significant effects on the percentages of abnormal spindle were observed. Correspondingly, the expressions of Nrf2, Atm, Atr, and Prkdc in IVM oocytes were markedly increased, following the inhibition of mTORC1 pathway by 10 nM rapamycin. Conclusion Rapamycin at 10 nM could ameliorate the developmental competence and quality of IVM oocytes of mice, mainly by improving the chromosome alignments. The inhibition of mTORC1 pathway, which involved in activating DDR-associated genes may act as a potential mechanism for oocyte quality improvement by rapamycin.

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出版当年[2021]版:
大类 | 2 区 医学
小类 | 2 区 内分泌学与代谢 2 区 生殖生物学
最新[2025]版:
大类 | 2 区 医学
小类 | 1 区 生殖生物学 2 区 内分泌学与代谢
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出版当年[2020]版:
Q1 REPRODUCTIVE BIOLOGY Q1 ENDOCRINOLOGY & METABOLISM
最新[2024]版:
Q1 ENDOCRINOLOGY & METABOLISM Q1 REPRODUCTIVE BIOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Reprod Med Ctr, 1095 Jiefang Rd, Wuhan 430030, Peoples R China
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