卵子细胞中介成熟受损含有增加的mtDNA删除
Jason D Kofinas1,2, Michelle L Seth-Smith3, Yael Kramer3
1Kofinas Fertility Group, 55 Central Park West, New York, NY, 10023, USA. Jason@kofinas.org.
Journal of assisted reproduction and genetics
|January 25, 2025
概括
人类卵子细胞中介性成熟受损,具有较高水平的线粒体DNA (mtDNA) 缺失. 这表明mtDNA删除会影响辅助生殖技术中的卵细胞质量和成熟成功.
科学领域:
- 生殖生物学 生殖生物学
- 细胞和分子生物学是细胞和分子生物学.
- 遗传学 是一个遗传学.
背景情况:
- 辅助生殖技术 (ART) 中的受控卵巢刺激旨在诱导介质能力.
- 线粒体DNA (mtDNA) 缺失在衰老的组织中积累,并且存在于人类卵细胞中.
- 产卵生成可能涉及从生殖线中去除有害的mtDNA缺失.
研究的目的:
- 调查卵细胞内在因素,特别是mtDNA缺失是否影响卵细胞成熟.
- 为了测试这种假设,介质性合格的卵子细胞比停止的卵子细胞具有较低的mtDNA删除水平.
- 为了分析体外受精 (IVF) 周期中人类卵细胞中的mtDNA删除比.
主要方法:
- 开发了一种新的实时PCR试验,以量化mtDNA总拷贝数 (mtDNACN) 和 mtDNA含有常见的5Kb删除.
- 对143个培养的人类卵细胞计算了mtDNA删除比 (mtDNADR).
- 克鲁斯卡尔-瓦利斯测试通过对卵细胞成熟阶段 (GV,MI,MII) 的mtDNACN和mtDNADR进行比较.
主要成果:
- 51.75%的卵细胞成熟到第二阶段 (MII),17%在第一阶段 (MI) 停产.
- 与GV (27.87%) 和MI (31.88%) 卵细胞相比,MII卵细胞 (20.05%) 的mtDNA删除比率平均显着较低 (分别p<0.001和p=0.034).
- 患者年龄与极体挤出时间正相关 (-0.278).
结论:
- 卵细胞表现出受损的介质成熟,表明mtDNA缺失的负担增加.
- 这项研究提供了第一个证据,将mtDNA删除比率与人卵细胞成熟 in vitro联系起来.
- 减少mtDNA完整性可能是ART中卵细胞成熟失败的一个因素.
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