Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice.

ABSTRACT: Ancestral environmental exposures to non-mutagenic agents can exert effects in unexposed descendants. This transgenerational inheritance has significant implications for understanding disease etiology. Here we show that exposure of F0 mice to the obesogen tributyltin (TBT) throughout pregnancy and lactation predisposes unexposed F4 male descendants to obesity when dietary fat is increased. Analyses of body fat, plasma hormone levels, and visceral white adipose tissue DNA methylome and transcriptome collectively indicate that the F4 obesity is consistent with a leptin resistant, thrifty phenotype. Ancestral TBT exposure induces global changes in DNA methylation and altered expression of metabolism-relevant genes. Analysis of chromatin accessibility in F3 and F4 sperm reveals significant dif

SUBMITTER: Chamorro-Garcia R 

PROVIDER: S-EPMC5722856 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature