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孕产妇的肥胖可能通过通过增加DNMTs诱导卵细胞基因组超甲基化来破坏后代的新陈代谢

Shuo Chao¹, Jun Lu¹, Li-Jun Li¹

¹College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, China.

|December 6, 2024

概括

孕产妇的肥胖会破坏卵细胞DNA甲基化,其影响可能会传给后代. 黑色素治疗通过通过cAMP/PKA/CREB通路调节DNA甲基转移酶来逆转这些变化.

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.
代谢学代谢学代谢学

背景情况:

孕产妇肥胖会对卵细胞DNA甲基化建立产生负面影响.
这些影响背后的精确分子机制尚未完全理解.

研究的目的:

为了研究母亲肥胖对卵细胞基因组甲基化的影响.
阐明黑激素在调解这些表观遗传变化的作用.
为了确定参与黑激素调节DNA甲基转移酶的信号通路.

主要方法:

利用高脂肪饮食 (HFD) 诱导的小鼠模型来模拟母亲的肥胖.
分析了卵细胞和F2代卵细胞/肝脏DNA甲基化模式.
进行了血清代谢组分析,以确定关键代谢物.
给予外源性黑激素和抑制/激活黑激素在卵细胞中的信号传递.
研究了cAMP/PKA/CREB路径.

主要成果:

孕产妇的肥胖导致卵细胞基因组甲基化发生显著干扰.
这些甲基化变化是部分可遗传到F2卵细胞和肝脏通过女性传播.
在肥胖的母亲中观察到血清黑激素水平降低.
外源性黑激素的使用使HFD诱导的卵细胞高甲基化正常化,并降低了DNA甲基转移酶 (DNMT3a,DNMT1) 表达.
黑色素通过cAMP/PKA/CREB通路调节DNMT的表达.

结论:

孕产妇肥胖会导致卵细胞的跨代表观遗传变化,部分由降低的黑色素水平介导.
黑色素在预防或逆转肥胖引起的卵细胞超甲基化方面发挥着至关重要的作用.
这种cAMP/PKA/CREB通路是黑素对卵细胞中DNA甲基转移酶的影响的关键调解者.

关键词:

通过DNA甲基化.在cAMP/PKA/CREB路径中.发育生物学是发展生物学.黑激素是什么意思黑激素是什么意思这里是鼠标鼠标鼠标鼠标鼠标鼠标.肥胖肥胖肥胖肥胖肥胖肥胖肥胖肥胖卵子细胞卵子细胞

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