TY - JOUR
T1 - In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism
AU - Radford, Elizabeth J.
AU - Ito, Mitsuteru
AU - Shi, Hui
AU - Corish, Jennifer A.
AU - Yamazawa, Kazuki
AU - Isganaitis, Elvira
AU - Seisenberger, Stefanie
AU - Hore, Timothy A.
AU - Reik, Wolf
AU - Erkek, Serap
AU - Peters, Antoine H.F.M.
AU - Patti, Mary Elizabeth
AU - Ferguson-Smith, Anne C.
PY - 2014/8/15
Y1 - 2014/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84906088773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906088773&partnerID=8YFLogxK
U2 - 10.1126/science.1255903
DO - 10.1126/science.1255903
M3 - Article
C2 - 25011554
AN - SCOPUS:84906088773
SN - 0036-8075
VL - 345
JO - Science
JF - Science
IS - 6198
M1 - 1255903
ER -
