肥胖会通过由肝脏衍生的异位体miR-122-5p诱导的莱迪格细胞铁死来损害精子生成
Nan Wang1, Boqi Zhang1, Tong Chen1
1College of Animal Sciences, Jilin University, Changchun, China.
Communications biology
|January 23, 2026
概括
高脂肪饮食通过改变外体载荷,特别是miR-122-5p,从而诱导莱迪格细胞铁亡并减少的产生,从而损害男性生育能力. 这突显了一条影响男性生殖健康的肝试管沟通通道.
科学领域:
- 生殖生物学 生殖生物学
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
背景情况:
- 肥胖与男性不孕症有关,通常是由于丸激素降低.
- 外基因组在繁殖中调解细胞通信,但它们在饮食诱导的不孕症中的作用尚不清楚.
- 高脂肪饮食 (HFD) 对外体载荷和激素生产的影响需要研究.
研究的目的:
- 为了研究外体在HFD诱导的降和小鼠受损的精子生成中的作用.
- 为了确定特定的外体载荷变化及其在肝-丸轴上的作用机制.
- 探索HFD诱导的男性不孕症的潜在治疗点.
主要方法:
- 从HFD和正常饮食小鼠中分离出血清外体.
- 异构体被转移到正常饮食小鼠中,以评估对丸激素和精子数量的影响.
- 使用了外体生物生成 (GW4869) 和铁 (Ferrostatin-1) 的抑制剂.
- 量化了肝脏和外体miR-122-5p水平.
- 在莱迪格细胞中分析了基CoA脱酶2 (SCD2) 表达.
主要成果:
- 在接受者小鼠中,转移HFD衍生的外体细胞降低了水平和精子数量.
- 外基因和铁灭抑制部分挽救了HFD诱导的精子发生障碍.
- 在HFD小鼠中,肝脏和外体 miR-122-5p 水平升高.
- 外体miR-122-5p通过抑制SCD2表达,降低合成,诱导莱迪格细胞铁.
结论:
- 来自肝脏的外体细胞在调解HFD诱导的降低和男性不孕症方面发挥着关键作用.
- 外体 miR-122-5p 是一个关键的媒介,诱导莱迪格细胞铁亡并损害精子生成.
- 向外体miR-122-5p或铁化可能为HFD相关的男性生殖功能障碍提供治疗策略.
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