In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism

Elizabeth J. Radford, Mitsuteru Ito, Hui Shi, Jennifer A. Corish, Kazuki Yamazawa, Elvira Isganaitis, Stefanie Seisenberger, Timothy A. Hore, Wolf Reik, Serap Erkek, Antoine H.F.M. Peters, Mary Elizabeth Patti, Anne C. Ferguson-Smith

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332 Citations (Scopus)

Abstract

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 F 1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated and enriched in nucleosome-retaining regions. A substantial fraction is resistant to early embryo methylation reprogramming, which may have an impact on F2 development. Differential methylation is not maintained in F2 tissues, yet locus-specific expression is perturbed. Thus, in utero nutritional exposures during critical windows of germ cell development can impact the male germline methylome, associated with metabolic disease in offspring.

Original languageEnglish
Article number1255903
JournalScience
Volume345
Issue number6198
DOIs
Publication statusPublished - 2014 Aug 15

ASJC Scopus subject areas

  • General

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    Radford, E. J., Ito, M., Shi, H., Corish, J. A., Yamazawa, K., Isganaitis, E., Seisenberger, S., Hore, T. A., Reik, W., Erkek, S., Peters, A. H. F. M., Patti, M. E., & Ferguson-Smith, A. C. (2014). In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science, 345(6198), [1255903]. https://doi.org/10.1126/science.1255903