Inheritance of perturbed methylation and metabolism caused by uterine malnutrition via oocytes.
Inheritance of perturbed methylation and metabolism caused by uterine malnutrition via oocytes.
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子宫营养不良通过卵母细胞遗传甲基化和代谢紊乱。
DOI：
10.1186/s12915-023-01545-x
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发表时间：
2023-02-24
期刊：
影响因子：
5.4
通讯作者：
Ge, Zhao-Jia
中科院分区：
文献类型：
--
作者：
Tang, Shou-Bin;Zhang, Ting-Ting;Yin, Shen;Shen, Wei;Luo, Shi-Ming;Zhao, Yong;Zhang, Cui-Lian;Klinger, Francesca Gioia;Sun, Qing-Yuan;Ge, Zhao-Jia
宫内营养不良对子代代谢有不良影响，但代谢性疾病代谢性传播的机制尚不清楚。在本研究中，我们发现子宫内营养不良导致雌性F1和F2在小鼠模型中的代谢紊乱。宫内营养不良导致F1代雌性代谢性疾病，并传染给F2代雌性。子宫内营养不良的F1代卵母细胞整体甲基化水平明显低于对照组。KEGG分析表明，启动子中具有差异甲基化区域(DMRS)的基因在代谢途径中显著丰富。在F2代组织中观察到位于代谢相关基因启动子位置的部分DMRS基因发生甲基化改变，这些基因的表达也发生了变化。同时，在F1卵母细胞中也观察到验证的DMRS在F2卵母细胞中的DNA甲基化异常。这些结果表明，DNA甲基化可能通过女性生殖系介导子宫内营养不良所致代谢紊乱的跨代遗传。网上版载有补充材料，可在10.1186/s12915-023-01545-x查阅。
Undernourishment in utero has deleterious effects on the metabolism of offspring, but the mechanism of the transgenerational transmission of metabolic disorders is not well known. In the present study, we found that undernourishment in utero resulted in metabolic disorders of female F1 and F2 in mouse model. Undernutrition in utero induced metabolic disorders of F1 females, which was transmitted to F2 females. The global methylation in oocytes of F1 exposed to undernutrition in utero was decreased compared with the control. KEGG analysis showed that genes with differential methylation regions (DMRs) in promoters were significantly enriched in metabolic pathways. The altered methylation of some DMRs in F1 oocytes located at the promoters of metabolic-related genes were partially observed in F2 tissues, and the expressions of these genes were also changed. Meanwhile, the abnormal DNA methylation of the validated DMRs in F1 oocytes was also observed in F2 oocytes. These results indicate that DNA methylation may mediate the transgenerational inheritance of metabolic disorders induced by undernourishment in utero via female germline. The online version contains supplementary material available at 10.1186/s12915-023-01545-x.
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影响因子：
4.5
作者：
Kobayashi H;Sakurai T;Imai M;Takahashi N;Fukuda A;Yayoi O;Sato S;Nakabayashi K;Hata K;Sotomaru Y;Suzuki Y;Kono T
通讯作者：
Kono T
影响因子：
64.5
作者：
Carone BR;Fauquier L;Habib N;Shea JM;Hart CE;Li R;Bock C;Li C;Gu H;Zamore PD;Meissner A;Weng Z;Hofmann HA;Friedman N;Rando OJ
通讯作者：
Rando OJ
影响因子：
3.7
作者：
Manikkam M;Haque MM;Guerrero-Bosagna C;Nilsson EE;Skinner MK
通讯作者：
Skinner MK
影响因子：
8.1
作者：
Holland WL;Xia JY;Johnson JA;Sun K;Pearson MJ;Sharma AX;Quittner-Strom E;Tippetts TS;Gordillo R;Scherer PE
通讯作者：
Scherer PE
影响因子：
1.9
作者：
Cogollos, Laura;Garcia-Contreras, Consolacion;Gonzalez-Bulnes, Antonio
通讯作者：
Gonzalez-Bulnes, Antonio