抑制ISG15可以防止因炎症而导致的卵巢衰老
Yaru Chen1,2, Xin Liu1, Yuyang Song1
1Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China.
概括
干扰素刺激基因15 (ISG15) 通过促进炎症,加速卵巢衰老和不孕症. 降低ISG15水平可以保护老年小鼠的卵巢功能和生育能力.
科学领域:
- 生殖生物学和衰老问题
- 免疫学和炎症的研究
背景情况:
- 炎症是衰老的关键因素,对卵巢功能和女性生育能力产生负面影响.
- 在卵巢衰老中,ISGylation (一种翻译后修饰) 的作用尚未完全理解,尽管它已知参与炎症和植入.
研究的目的:
- 调查ISG15在与年龄相关的卵巢功能下降和女性生育能力方面的作用.
- 阐明ISG15影响卵巢衰老和炎症的分子机制.
主要方法:
- 在小鼠卵巢中对Isg15的年龄依赖表达分析.
- 评估卵巢储备,内分泌功能和野生类型和Isg15敲击小鼠的生育能力.
- 来自Isg15淘汰赛和野生型小鼠的卵巢的转录组测序.
- 对ISG15-PSMD14-IL-1β信号通路的研究.
主要成果:
- 在小鼠卵巢中,Isg15的表达随着年龄的增长而增加,与生育能力的降低相关.
- Isg15敲除部分挽救了与年龄相关的生育能力下降和卵巢功能障碍.
- Isg15 缺失改善了炎症,氧化应激,并保护了老化卵巢中的线粒体功能.
- ISG15通过降解PSMD14来促进IL-1β的成熟,PSMD14是炎症酶激活的负调节器.
结论:
- ISG15通过增强炎症,加速卵巢颗粒细胞衰老,从而减少生殖寿命.
- ISG15-PSMD14-IL-1β轴是一个新的途径,可以激活卵巢衰老中的炎症.
- 缺少Isg15可以通过减少卵巢炎症来缓解与年龄相关的女性不孕症,从而成为潜在的治疗点.
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