下丘脑FTO-IGF2BP2-介导m6A调节ANXA2:一种新型轴,防止HS诱导的精子运动率下降
Bin Li1, Ruixi Ming2, Guobin Qiu2
1Institute of Comparative Medicine, College of Veterinary, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 225009, Yangzhou, Jiangsu, China; Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, 66421, Homburg, Germany.
International journal of biological macromolecules
|December 8, 2025
概括
热应激通过减少下丘脑FTO表达来损害男性生育能力,导致炎症和激素抑制. 恢复FTO使激素水平正常化并改善精子质量,为热应激不孕症提供治疗点.
科学领域:
- 生殖生物学 生殖生物学
- 神经内分泌学神经内分泌学
- 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:
- 全球热应激 (HS) 对男性生殖健康构成重大威胁.
- 导致HS引起的男性不孕不育的神经内分泌机制尚未完全理解.
研究的目的:
- 调查N6-甲基氨酸 (m6A) 脱甲酸FTO在热应激期间在下丘脑中的作用.
- 阐明将中央神经炎症与男性不孕症联系起来的分子途径.
主要方法:
- 利用小鼠和猪模型研究热应激的影响.
- 采用lentiviral基因传递来恢复在下丘脑中的FTO表达.
- 分析了下丘脑基因表达,质激活,血脑屏障完整性,荷尔蒙水平,丸组织学和精子参数.
主要成果:
- 热应激降低了下丘脑FTO,导致m6A高甲基化,质激活,BBB干扰和抑制生殖激素分泌.
- 恢复FTO正常化激素水平,减少神经炎症,保持BBB完整性,改善丸功能和精子运动性.
- 确定了一种涉及FTO,IGF2BP2和ANXA2mRNA的机制,调节下丘脑脂质代谢和炎症.
结论:
- 保守的下丘脑FTO-IGF2BP2-ANXA2表转录轴将中枢神经炎症与男性生殖健康联系起来.
- 针对这一轴,为热应激诱导的男性不孕症提供了潜在的治疗策略.
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