嗅觉受体Olfr25通过CatSper-Ca2+信号通路调解由低剂量双A诱导的精子功能障碍
Jing Gu1, Ning Zhang1, Xiao Jiang1
1State Key Lab of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing 400038, China.
Toxics
|June 26, 2024
概括
低剂量的双A (BPA) 通过降低运动性和体反应来损害精子功能. 嗅觉受体Olfr25通过CatSper-信号通路在这种功能障碍中发挥作用.
科学领域:
- 生殖毒理学 生殖毒理学
- 内分泌学 在内分泌学.
- 精子生物学 精子生物学
背景情况:
- 双A (BPA) 是一种内分泌干扰物,已知对男性生殖有不良影响.
- 低剂量BPA对男性生殖功能的毒性的具体机制仍然不完全理解.
研究的目的:
- 调查低剂量双A (BPA) 暴露对雄性小鼠生殖参数的毒性影响和潜在机制.
- 为了确定潜在的分子通路和基因参与BPA诱导的精子功能障碍.
主要方法:
- 昆明雄性小鼠被暴露在低剂量的BPA (0.03,0.3,3 mg/kg/d) 中,持续了10周.
- 评估了精子的功能参数 (机动性,化学反应,体反应).
- 实验室模型,奥米克分析和基因表达研究 (Olfr25,CatSper子单元) 用于阐明机制.
主要成果:
- 低剂量的BPA显著降低了精子的运动性,化疗和体反应,但没有引起显著的丸形态变化.
- 奥米克斯分析发现了与嗅觉受体相关的通路的丰富.
- 在BPA暴露后观察到Olfr25嗅觉受体基因和CatSper通道子单元的mRNA水平降低.
- 奥尔弗25的淘汰影响了离子水平和CatSper表达,而奥尔弗25的过度表达部分挽救了BPA诱导的影响.
结论:
- 低剂量的BPA诱导精子功能障碍,可能通过嗅觉受体Olfr25及其对CatSper-Ca2+信号通路的影响.
- 在BPA诱导的精子功能的损害中,Olfr25可能是关键的调解者.
- 这项研究为低剂量BPA对男性生育能力的毒性分子机制提供了新的见解.
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