Environmentally induced epigenetic inheritance of sperm epimutations and disease: exposure and disease diagnostics in sperm

Abstract

Epigenetic alterations of sperm due to effects of environmental toxicants, nutrition or stress significantly amplify the impact and health hazards of these exposures. One of the most sensitive periods to exposure is during fetal gonadal sex determination when the germ line is undergoing epigenetic programming and DNA re-methylation occurs, however, adult exposures have also been shown to impact sperm epimutations. Previous studies have shown that endocrine disruptors can cause an increase in adult onset disease such as infertility, prostate, ovary and kidney disease, cancers and obesity. Interestingly, this effect is transgenerational (F1, F2, F3 and F4 generations) and hypothesized to be due to a permanent (imprinted) altered DNA methylation of the germ-line. The transgenerational epigenetic mechanism appears to involve the actions of an environmental compound to permanently alter the epigenetic (e.g. DNA methylation) programming of the germ line that then alters the transcriptomes of developing organs to induce disease susceptibility and development transgenerationally. In addition to DNA methylation, alterations in sperm ncRNAs have also been observed. A variety of different environmental compounds have been shown to induce this epigenetic transgenerational inheritance of disease including: fungicide vinclozolin, plastics BPA and phthalates, pesticides, DDT, dioxin, hydrocarbons, and chemotherapies. Interestingly, exposure specific epigenetic alterations were observed between the specific exposures. The suggestion that environmental factors can reprogram the germ line to induce epigenetic inheritance of disease is a new paradigm in disease etiology that is particularly relevant to preconception diagnostics of sperm.