Abstract
Environmental compounds can promote epigenetic
transgenerational inheritance of adult-onset disease in subsequent generations
following ancestral exposure during fetal gonadal sex determination. The
current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin,
TCDD) to promote epigenetic transgenerational inheritance of disease and DNA
methylation epimutations in sperm. Gestating F0 generation females were exposed
to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1
and F3 generation rats. The incidences of total disease and multiple disease
increased in F1 and F3 generations. Prostate disease, ovarian primordial
follicle loss and polycystic ovary disease were increased in F1 generation
dioxin lineage. Kidney disease in males, pubertal abnormalities in females,
ovarian primordial follicle loss and polycystic ovary disease were increased in
F3 generation dioxin lineage animals. Analysis of the F3 generation sperm
epigenome identified 50 differentially DNA methylated regions (DMR) in gene
promoters. These DMR provide potential epigenetic biomarkers for
transgenerational disease and ancestral environmental exposures. Observations
demonstrate dioxin exposure of a gestating female promotes epigenetic
transgenerational inheritance of adult onset disease and sperm epimutations.
journal reference (Open Access): PLoS ONE >>