后代的端粒长度是由受精时的线粒体-核通信决定的
Yasmyn E Winstanley1, Ryan D Rose1,2, Alexander P Sobinoff3
1Robinson Research Institute, School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia.
Nature communications
|March 15, 2025
概括
早期生命中的端粒长度,对与衰老相关的疾病风险至关重要,由细胞质中的线粒体活动调节. 破坏线粒体功能或诸如母亲肥胖等因素会损害端粒延长,但治疗可以恢复端粒长度.
科学领域:
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
- 线粒体生物学 线粒体生物学
背景情况:
- 在生命早期设置的端粒长度会影响与衰老相关的疾病风险.
- 调节端粒长度遗传及其可修改性的生物信号尚未得到充分理解.
研究的目的:
- 研究线粒体活动在调节生命早期端粒长度中的作用.
- 确定在植入前发育过程中端粒长度重置是否可修改.
主要方法:
- 使用20%O2或罗诺的小鼠囊中线粒体活动的破坏.
- 测定8细胞和芽细胞阶段的端粒长度,包括细胞内部质量 (ICM).
- 评估孕产妇肥胖和晚年孕产妇对胚胎线粒体反应性氧物种 (mtROS) 和端粒延长的影响.
- 应用线粒体向治疗药物 (BGP-15,MitoQ,SS-31,甲胺) 来调节植入前端粒重置.
主要成果:
- 异构体中线粒体活动受到干扰会损害8细胞和胚胎细胞阶段之间的端粒延长.
- 在ICM中观察到更短的端粒,并在器官生成后持续存在.
- 卵巢中mtROS升高与母亲肥胖或晚年相关,导致类似的端粒延长缺陷.
- 在ICM形成期间的端粒体延长是由受精时的线粒体-核通信控制的.
- 线粒体向治疗成功调节了植入前端粒重置,并恢复了新生儿端粒长度缺陷.
结论:
- 生命早期的线粒体活动对于确定端粒长度至关重要.
- 肥胖和年龄等母亲因素通过线粒体通路影响胚胎端粒长度.
- 植入前端粒重置是治疗干预的可针对性过程,以纠正端粒长度缺陷.
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