母亲对雄激素的暴露会通过父亲的遗传诱导代际影响
Yu Zhou1,2, Chao Lian1, Yingfei Lu1
1Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.
The Journal of endocrinology
|May 28, 2024
概括
在小鼠中,母体丸激素暴露会导致子孙跨代的多囊性卵巢综合征 (PCOS) 状况. 这通过雄性小鼠的表观遗传变化发生,影响雌性后代.
科学领域:
- 生殖生物学 生殖生物学
- 内分泌学 在内分泌学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 多囊卵巢综合征 (PCOS) 是一种复杂的内分泌疾病,其病因不明.
- 产前对雄激素的暴露是可疑导致PCOS发展的因素.
- 越来越多地认识到环境暴露的代际影响.
研究的目的:
- 为了研究母体丸激素暴露后小鼠中PCOS类型表型的代际遗传.
- 探索涉及这种遗传的潜在分子机制,包括表观遗传修饰.
主要方法:
- 在F0小鼠中的母体丸激素暴露.
- 对F1雄性和F2雌性后代的血清激素水平和生殖系统发育的评估.
- 在相关组织中分析N6-甲基亚丁素 (m6A) 修饰,mRNA甲基化和蛋白质表达.
- 对mTOR和FoxO3信号通路的研究.
主要成果:
- 产前丸激素暴露导致F1男性和F2女性的血清激素水平和生殖发育受损.
- 在F1男性丸中下调的m6A机器导致mRNA低甲基化,包括Fzd6.
- 在F2雌性卵巢中减少的FZD6蛋白抑制了mTOR信号传递和激活了FoxO3酸化,损害了卵泡发育.
结论:
- 孕产妇暴露于丸激素可以通过男性后代在后代诱导类似PCOS的表型.
- 表观遗传修饰,特别是改变的m6A甲基化,通过FZD6影响mTOR信号通路,与这一代际传播有关.
- 这些发现突显了表观遗传机制在跨代传播环境诱导的生殖障碍方面的作用.
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