在长期暴露于甲的老鼠中,GRPR下调抑制通过PLCβ/IP3R信号通路介导的Ca2+抑制精子生成
Yan-Qi Yang1, Rui-Fang Sun1, Pan Ge1
1Department of Pathology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Shaanxi, 710061, China; Institute of Genetics and Developmental Biology, Xi'an Jiaotong University, Shaanxi, 710061, China.
概括
甲暴露会通过破坏GRPR/PLCβ/IP3R通路而损害老鼠精子质量,影响水平和细胞功能. 恢复GRPR可以部分扭转这些有害影响.
科学领域:
- 生殖毒理学 生殖毒理学
- 环境健康 环境健康
- 细胞生物学 细胞生物学
背景情况:
- 甲 (FA) 是一种与男性不孕症相关的空气污染物.
- 由于FA引起的男性不孕不育的确切机制尚未完全理解.
研究的目的:
- 在大鼠中研究甲诱导的男性不孕症背后的分子机制.
- 探索GRPR及其相关信号通路在精子生成细胞中的作用.
主要方法:
- 雄性Sprague-Dawley大鼠在八周内暴露在不同水平的甲中.
- 使用了组织学分析 (HE染色,精子涂抹),qRT-PCR,西斑和分子对接 (ZDOCK).
- 细胞增殖 (CCK8),细胞内度 (Fluo 3-AM) 和细胞灭亡 (流细胞计) 被评估.
主要成果:
- 甲暴露导致小鼠的精子质量下降和精子受损.
- 在暴露的老鼠的丸组织和精子细胞中,GRPR表达显著下调.
- 甲抑制了GRPR,PLCβ和IP3R,减少了细胞内,抑制了增殖,并诱导了精子生成细胞的亡.
- 促进GRPR部分挽救了这些影响,突出了它在PLCβ/IP3R通路中的作用.
结论:
- 通过介导的PLCβ/IP3R信号通路,GRPR在精子生成中发挥着至关重要的作用.
- 甲通过干扰这种途径来破坏男性的生殖功能.
- 针对GRPR/PLCβ/IP3R通路可能为甲诱导的男性不孕症提供治疗潜力.
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