通过卵细胞TET3缺陷遗传的葡萄糖不耐受
Bin Chen1,2,3, Ya-Rui Du3, Hong Zhu4,5
1Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Nature
|May 18, 2022
概括
母胎高血糖会增加后代的数量
科学领域:
- 生殖生物学
- 内分泌学
- 表观遗传学
背景情况:
- 糖尿病影响了许多生育年龄的妇女.
- 孕期糖尿病对后代的健康有长期影响.
- 孕期糖尿病对后代成人疾病风险的影响还没有得到充分研究.
研究的目的:
- 调查妊娠期糖尿病与后代葡萄糖不耐受之间的联系.
- 探索TET3二氧化酶在这种母体效应中介作用.
- 确定可能的孕前干预措施.
主要方法:
- 使用过高血糖的小鼠模型 (HG小鼠) 和人类样本.
- 在卵细胞中评估了TET3二氧化酶表达.
- 分析了胰岛素分泌基因的DNA甲基化模式.
- 对后代的葡萄糖稳定性和表观遗传标记进行了检查.
主要成果:
- 在HG小鼠和患有糖尿病的人类卵细胞中减少了TET3表达.
- 卵细胞TET3不足导致父性胰岛素基因 (例如Gck) 的高甲基化.
- 这种表观遗传变化持续存在,导致后代的葡萄糖稳定性受损和胰岛素分泌缺陷.
- 在小鼠中,母体的Tet3删除重现了这些效应,而外源的Tet3mRNA则改善了这些效应.
结论:
- 孕期高血糖会使后代在卵细胞发育过程中通过TET3不足产生葡萄糖不耐受.
- 这种表观遗传机制,而不是直接的卵细胞干扰,是母体效应的基础.
- 针对母亲健康的孕前干预措施可以保护后代的代谢健康.
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