Embryonic defects induced by maternal obesity in mice derive from Stella insufficiency in oocytes

Longsen Han, Chao Ren, Ling Li, Xiaoyan Li, Juan Ge, Haichao Wang, Yi Liang Miao, Xuejiang Guo, Kelle H. Moley, Wenjie Shu, Qiang Wang

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32 Scopus citations

Abstract

Maternal obesity can impair embryo development and offspring health, yet the mechanisms responsible remain poorly understood. In a high-fat diet (HFD)-based female mouse model of obesity, we identified a marked reduction of Stella (also known as DPPA3 or PGC7) protein in oocytes. Starting with this clue, we found that the establishment of pronuclear epigenetic asymmetry in zygotes from obese mice was severely disrupted, inducing the accumulation of maternal 5-hydroxymethylcytosine modifications and DNA lesions. Furthermore, methylome-wide sequencing analysis detected global hypomethylation across the zygote genome in HFD-fed mice, with a specific enrichment in transposon elements and unique regions. Notably, overexpression of Stella in the oocytes of HFD-fed mice not only restored the epigenetic remodeling in zygotes but also partly ameliorated the maternal-obesity-associated developmental defects in early embryos and fetal growth. Thus, Stella insufficiency in oocytes may represent a critical mechanism that mediates the phenotypic effects of maternal obesity in embryos and offspring.

Original languageEnglish
Pages (from-to)432-442
Number of pages11
JournalNature Genetics
Volume50
Issue number3
DOIs
StatePublished - Mar 1 2018

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    Han, L., Ren, C., Li, L., Li, X., Ge, J., Wang, H., Miao, Y. L., Guo, X., Moley, K. H., Shu, W., & Wang, Q. (2018). Embryonic defects induced by maternal obesity in mice derive from Stella insufficiency in oocytes. Nature Genetics, 50(3), 432-442. https://doi.org/10.1038/s41588-018-0055-6