改变的m6A修饰涉及YAP介导的亡反应在4-乙烯基二氧化诱导的卵子毒性
Yang Li1, Meifang Li2, Jian Liu1
1Department of Gynaecology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, China.
Ecotoxicology and environmental safety
|July 2, 2023
概括
在老鼠中,暴露于4-乙烯基环二氧化物 (VCD) 诱导过早的卵巢缺陷 (POI) 通过减少卵巢卵泡和改变N6-甲基氨酸 (m6A) RNA修饰. 这项研究揭示了m6A修饰变化,为POI机制和潜在的治疗点提供了洞察力.
科学领域:
- 生殖生物学 生殖生物学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 4-乙烯基环二氧化物 (VCD) 是一种工业化学物质,与早产卵巢衰竭 (POI) 和生殖功能衰竭有关.
- VCD诱导的老鼠模型模仿了自然的更年期,这使得它对研究生殖系统变化非常有价值.
研究的目的:
- 在VCD诱导的POI大鼠模型中研究卵泡损失的机制.
- 探索VCD暴露对卵巢之外的系统的影响.
- 检查N6-甲基氨酸 (m6A) RNA修饰在VCD诱导的POI中的作用.
主要方法:
- 雌性Sprague-Dawley大鼠被给予VCD (160毫克/公斤) 持续15天.
- 评估了生殖参数,神经内分泌功能,性激素水平和m6ARNA修饰水平.
- 在接受VCD治疗和对照大鼠的毛囊数和m6A水平进行了比较.
主要成果:
- 暴露于VCD导致不规则的雌性周期,并显著减少了原始,前腔和腹腔毛囊的数量.
- 毛囊刺激激素 (FSH) 水平增加,而抗穆勒尔激素 (AMH) 水平在接受VCD治疗的老鼠中降低.
- 总m6A水平显著下降,在ALKBH5-介导的YAP m6A修饰中显著变化.
结论:
- 在大鼠中,VCD诱导的POI与显著的卵泡枯竭和改变的性激素配置相关.
- 在这个POI模型中,N6-甲基氨酸 (m6A) RNA修饰显著失调.
- 这项研究为m6A修饰在卵泡发育中的作用提供了新的见解,并建议POI的潜在治疗点.
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