核糖体失调和干预与年龄相关的不孕症
Jie Li1, Honghong Wang2, Pengfei Zhu2
1State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Department of Cell Biology and Genetics, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Cell reports. Medicine
|October 28, 2025
概括
女人的生育能力随着年龄的增长而下降,这是由于卵子和累积细胞的分子变化. 核糖体基因转录增加,但拉巴胺治疗显示有望改善老年妇女的妊娠结果.
科学领域:
- 生殖生物学 生殖生物学
- 分子遗传学 分子遗传学
- 老年学是一门学科.
背景情况:
- 女人的生育能力自然会随着年龄的增长而下降.
- 与年龄相关的不孕不育背后的分子机制尚未完全理解.
- 老年女性无法解释的不孕症是一个重大的临床挑战.
研究的目的:
- 研究女性年龄相关不孕症的分子基础.
- 为了确定与衰老相关的卵细胞和累积细胞的特定细胞和分子变化.
- 评估拉巴胺在治疗与年龄相关的不孕症中的治疗潜力.
主要方法:
- 从30多岁中期的女性获得的卵细胞和累积细胞的转录组分析.
- 基因表达的分析与中变,蛋白质稳态和核糖体生物发生有关.
- 评估DNA甲基化和异色素蛋白模式.
- 在体外用拉巴胺素治疗及其对细胞过程影响的评估.
- 拉帕米辛在接受体外受精 (IVF) 的患者的临床应用.
主要成果:
- 在老化卵细胞和累积细胞中观察到的核糖体基因转录的增加.
- 降低老化卵细胞中中变质基因,活性蛋白和凝聚素成分的下调.
- 在老化的累积细胞中,溶酶体和蛋白质静止的破坏.
- 在DNA低甲基化,改变的异质染色素和增加的核糖体基因转录之间的联系.
- 拉巴胺治疗改善了蛋白质平衡,并导致不育患者的高质量囊胚和成功怀孕.
结论:
- 高水平的核糖体基因转录在与年龄相关的不孕症中起着因果作用.
- 介质变化,蛋白质稳定和表观遗传调节的破坏有助于随着年龄的增长降低生育能力.
- 拉帕米辛是一种有前途的治疗剂,可以改善与年龄相关的不孕症和复发性IVF失败的妇女的妊娠结果.
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