蛋白二硫化异硫酶对于小鼠的精子发生是必不可少的
Yaqiong Zhang1, Aizhen Yang1, Zhenzhen Zhao1
1National Clinical Research Center for Hematologic Diseases, Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
JCI insight
|June 24, 2024
概括
蛋白二硫化异构酶 (PDI) 对男性生育能力至关重要. 在小鼠中,PDI缺乏导致精子生成受损,导致由于蛋白质质量控制缺陷和生殖细胞亡而导致不孕.
科学领域:
- 生殖生物学 生殖生物学
- 分子细胞生物学 分子细胞生物学
- 生物化学 生物化学
背景情况:
- 精子生成依赖于细胞内网膜 (ER) 蛋白质的稳态,但基本机制尚不清楚.
- 蛋白质二硫化异构酶 (PDI) 酶是催化二硫化键形成的关键参与者,用于ER内的新生蛋白质.
研究的目的:
- 研究PDI家族酶在精子生成中的作用.
- 阐明PDI影响男性生育能力的分子机制.
主要方法:
- 产生和分析14个缺少PDI家族酶的淘汰赛 (KO) 鼠标菌株.
- 在缺乏PDI的小鼠中评估丸组织学,生殖细胞数,精子参数和生育能力.
- 通过定量质谱学分析ER压力标志物,与亡相关的蛋白质,DNA修复和蛋白质表达.
主要成果:
- 选择性PDI缺乏导致显著的精子生成缺陷,包括生殖细胞损失,丸缩,寡精和完全的男性不育.
- 缺少PDI的精子细胞表现出高调的ER压力和亡标志物,增加细胞死亡,延迟DNA双链断裂修复,以及不适当的交叉.
- 定量质谱检测显示,PDI缺乏的丸中,精子生成必不可少的蛋白质 (HSPA4L,SHCBP1L,DDX4) 的下调,而PDI直接氧化SHCBP1L.
结论:
- 在小鼠的精子生成过程中,PDI对于维持蛋白质质量控制至关重要.
- 作为一种硫醇氧化酶,PDI的功能对于SHCBP1L等关键精子生成蛋白中二硫化键的正确形成至关重要.
- 干扰PDI功能导致ER压力,亡,最终导致男性不孕.
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