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维生素C通过调节PTEN/PI3K/AKT轴来挽救由母亲Kdm2a缺乏引起的胚胎发育停滞

Qinhui Yang¹, Yumian Xie¹, Ying Cen²

¹Key Laboratory for Animal Science of National Ethnic Affairs Commission, Southwest Minzu University, Chengdu, 610041, PR China; Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Reservation and Utilization, Ministry of Education and Sichuan Province, Southwest Minzu University, Chengdu, 610041, PR China.

|November 5, 2025

概括

维生素C (VC) 补充剂通过增强胚胎发育和减少亡,改善了Kdm2a缺乏的小鼠的生殖结果. VC促进表观遗传重编程,为KDM2A相关的生殖问题提供潜在的治疗方法.

科学领域:

生殖生物学生殖生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
发展生物学发展生物学

背景情况:

植入前胚胎的发育依赖于精确的表观遗传调节,包括基因素修饰和DNA甲基化.
基因组脱甲基酶KDM2A对卵细胞成熟和胚胎发育至关重要,但其缺乏会导致生殖问题.
纠正KDM2A缺陷引起的生殖问题的机制尚不清楚.

研究的目的:

调查维生素C (VC) 在改善由母体Kdm2a缺乏引起的生殖能力下降方面的疗效.
阐明VC在Kdm2a缺陷胚胎中影响早期胚胎发育的分子机制.

主要方法:

在Kdm2a条件淘汰赛 (cKO) 时,小鼠接受了VC治疗.
评估了生殖参数,包括植入和 litter 大小.
用RT-qPCR,TUNEL测定,免疫光和Smart-seq来分析基因表达,细胞亡,基因素修饰,DNA甲基化和信号通路.

主要成果:

在Kdm2a cKO小鼠中,VC治疗显著改善了生殖能力,增加了植入和 litter 数量.
VC抑制了胚胎亡并增强了干性基因表达.
在Kdm2a cKO胚胎中,VC促进了DNA脱甲基化和调节的组素修饰 (H3K36me1/2).
它通过PTEN/PI3K/AKT信号通路调节了早期胚胎发育.

结论:

补充维生素C有效地挽救与母亲Kdm2a缺乏相关的生殖缺陷.
维基基因通过促进胚胎质子和DNA脱甲基和调节关键的发育信号通路而起作用.
VC代表了与KDM2A异常相关的生殖障碍的潜在治疗策略.

关键词:

通过DNA甲基化.基因组胺基因的修改 Kdm2a cKO 的时间在PTEN/PI3K/AKT轴上维生素C 维生素C是一种

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