过高的N-糖基化甲素L会损害卵细胞功能,并在生殖衰老过程中导致卵细胞衰老
Kemei Zhang1, Rui Xu2, Lu Zheng2
1Department of Reproductive Medicine, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, China.
Aging cell
|November 4, 2024
概括
卵巢老化和卵细胞质量下降与高甲素L (Ctsl) 水平有关. 抑制或减少Ctsl可以改善卵细胞质量和生殖潜力,为延缓卵巢衰老提供了目标.
科学领域:
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
- 老年学是一门学科.
背景情况:
- 女性不孕不育通常与与年龄相关的卵细胞质量和卵巢功能下降有关.
- 导致卵巢衰老和卵细胞衰老的精确分子机制尚未完全理解.
- N-糖蛋白在卵巢衰老中发挥作用,但它们的具体贡献需要进一步研究.
研究的目的:
- 调查N-糖蛋白,特别是甲素L (Ctsl) 在卵巢衰老和卵细胞衰老中的作用.
- 确定Ctsl水平及其N221糖化对卵细胞质量的影响.
- 评估向Ctsl的治疗潜力,以改善卵细胞质量和生殖结果.
主要方法:
- 在不同生殖年龄的小鼠的卵巢中对N-糖的比较分析.
- 在年轻和老化的卵细胞中量化Ctsl水平.
- 卵细胞中Ctsl的过度表达和局部定向的突变发生.
- 评估卵细胞质量参数,包括线粒体功能,活性氧物种 (ROS) 水平,亡和溶酶体容量.
- 使用药理抑制剂抑制Ctsl活性.
- 使用小干扰RNA (siRNA) 微注射降低Ctsl表达的调节.
- 评估受精率和治疗卵细胞中的胚胎细胞形成.
主要成果:
- 在生殖年龄小鼠的卵巢中观察到甲素L (Ctsl) 的N221糖的显著增加.
- 陈旧的卵细胞表现出明显升高的Ctsl水平.
- 野生型Ctsl在年轻卵细胞中的过度表达降低了其质量,而N221-glycosylation突变体则没有.
- 在老化的卵细胞中抑制CTSL改善了线粒体功能,减少了ROS和亡,并恢复了溶酶体容量.
- 在老化的卵细胞中,siRNA介导的Ctsl knockdown提高了受精率和胚胎细胞形成率.
结论:
- 升高的N-糖基化CTSl表达有助于卵细胞质量下降和衰老.
- Ctsl 的 N221 糖化位点对于其对卵细胞健康的有害影响至关重要.
- 向Ctsl活动或表达是一种有前途的治疗策略,可以缓解卵巢衰老并改善卵细胞活力.
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