卵母细胞介导的子宫营养不足引起的甲基化和代谢紊乱的遗传。

Inheritance of perturbed methylation and metabolism caused by uterine malnutrition via oocytes.

机构信息

College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, 266109, People's Republic of China.

Reproductive Medicine Center, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, 450003, People's Republic of China.

出版信息

BMC Biol. 2023 Feb 24;21(1):43. doi: 10.1186/s12915-023-01545-x.

DOI:10.1186/s12915-023-01545-x

PMID:36829148

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9960220/

Abstract

BACKGROUND

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.

RESULTS

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.

CONCLUSIONS

These results indicate that DNA methylation may mediate the transgenerational inheritance of metabolic disorders induced by undernourishment in utero via female germline.

摘要

背景

宫内营养不良对后代的代谢有有害影响，但代谢障碍的跨代传递机制尚不清楚。本研究发现，宫内营养不良导致了小鼠模型中 F1 和 F2 代雌性的代谢紊乱。

结果

宫内营养不良导致 F1 代雌性出现代谢紊乱，并传递给 F2 代雌性。与对照组相比，暴露于宫内营养不良的 F1 卵母细胞的整体甲基化水平降低。KEGG 分析显示，启动子中具有差异甲基化区域（DMR）的基因在代谢途径中显著富集。F1 卵母细胞中一些 DMR 的甲基化改变位于代谢相关基因的启动子中，在 F2 组织中也观察到部分改变，这些基因的表达也发生了变化。同时，在 F2 卵母细胞中也观察到 F1 卵母细胞中经验证的 DMR 的异常 DNA 甲基化。