Genomics

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Perturbed adult sperm methylome after in utero undernutrition is associated with transmission of metabolic disease


ABSTRACT: The pre and postnatal environment can affect both an individual’s risk of adult onset metabolic disease and that of subsequent generations. Although animal models and epidemiological data implicate epigenetic inheritance, little is known of the mechanisms involved. In a robust intergenerational model of developmental programming we demonstrate that the nutritional environment experienced in utero by F1 generation embryos alters the DNA methylome of the F1 adult male germ line in a locus-specific manner, without affecting overall methylation levels. Differentially methylated regions are mostly hypomethylated and are enriched in nucleosome retaining regions in adult sperm. A substantial fraction is resistant to early embryo methylation reprogramming, and thus have the potential to alter F2 generation development. Altered expression of transcripts neighbouring differentially methylated regions are evident in tissues of F2 offspring despite lack of persistence of differential methylation. Transmitted methylation variation in the germline at key regulatory loci may therefore contribute to the development of metabolic disease in the subsequent generation. 2 biological replicates of pooled sperm samples for each control (C) or undernutrition (UN) model

ORGANISM(S): Mus musculus  

SUBMITTER: Jennifer Corish  Elizabeth J Radford   Mary-Elizabeth Patti   Elvira Isganaitis   Hui Shi   Serap Erkek   Kazuki Yamazawa   Timothy Hore   Mitsiteru Ito   Stefanie Seisenberger   Antoine Peters   Wolf Reik   Anne C Ferguson-Smith    

PROVIDER: E-GEOD-58747 | ArrayExpress | 2014-07-16

SECONDARY ACCESSION(S): GSE58747SRP043514PRJNA253334

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism.

Radford Elizabeth J EJ   Ito Mitsuteru M   Shi Hui H   Corish Jennifer A JA   Yamazawa Kazuki K   Isganaitis Elvira E   Seisenberger Stefanie S   Hore Timothy A TA   Reik Wolf W   Erkek Serap S   Peters Antoine H F M AHFM   Patti Mary-Elizabeth ME   Ferguson-Smith Anne C AC  

Science (New York, N.Y.) 20140710 6198


Adverse prenatal environments can promote metabolic disease in offspring and subsequent generations. Animal models and epidemiological data implicate epigenetic inheritance, but the mechanisms remain unknown. In an intergenerational developmental programming model affecting F2 mouse metabolism, we demonstrate that the in utero nutritional environment of F1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated  ...[more]

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