Transgenerational neuroendocrine disruption of reproduction

Abstract

Exposure to endocrine disrupting chemicals (EDCs) is associated with dysfunctions of metabolism, energy balance, thyroid function and reproduction, and an increased risk of endocrine cancers. These multifactorial disorders can be ‘programmed’ through molecular epigenetic changes induced by exposure to EDCs early in life, the expression of which may not manifest until adulthood. In some cases, EDCs have detrimental effects on subsequent generations, which indicates that traits for disease predisposition may be passed to future generations by nongenomic inheritance. This Review discusses current understanding of the epigenetic mechanisms that underlie sexual differentiation of reproductive neuroendocrine systems in mammals and summarizes the literature on transgenerational epigenetic effects of representative EDCs: vinclozolin, diethylstilbesterol, bisphenol A and polychlorinated biphenyls. The article differentiates between context-dependent epigenetic transgenerational changes—namely, those that require environmental exposure, either via the EDC itself or through behavioral or physiological differences in parents—and germline-dependent epigenetic mechanisms. These processes, albeit discrete, are not mutually exclusive and can involve similar molecular mechanisms including DNA methylation and histone modifications and may predispose exposed individuals to transgenerational disruption of reproductive processes. New insights stress the crucial need to develop a clear understanding of how EDCs may program the epigenome of exposed individuals and their descendants.

Smoking induces differential miRNA expression in human spermatozoa: A potential transgenerational epigenetic concern?

“…A recent study has also detected miRNAs, together with other ncRNAs, such and other environmental chemical exposures. 4,6,20,51 Pathway analysis therefore suggests that miRNA-mediated perturbation of cell death and apoptosis by cigarette smoke is an important mechanism of toxicity, which may compromise sperm quality and/or early embryo development, and lead to disorders such as reproductive defects in the descendants of smokers.…”

Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs

“…The F3 phenotype can be unequivocally defined as a transgenerational phenomenon for an embryonic exposure (Skinner, 2008). There are various studies revealed that the epigenetic changes in the germline induced by EDCs could result in transgenerational inheritance of adverse effects, especially the male reproductive system (Walker and Gore, 2011). These detrimental effects on subsequent generations can be possibly "programmed" through molecular epigenetic changes induced by ancestral exposure to EDCs, the expression of which may not manifest until adulthood (Anway et al, 2005;Stouder and Paoloni-Giacobino, 2010).…”

Effect of perinatal exposure to Bisphenol-A on DNA methylation and histone acetylation in cerebral cortex and hippocampus of postnatal male mice

“…Developmental exposure to BPA in rodents showed negative impact on fertility, reproduction, behavior and increasing risk of obesity (Migliarini et al, 2011;Walker and Gore, 2011;Wolstenholme et al, 2012;Nagao et al, 2014). The developing brain is highly sensitive to the changes of environmental conditions such as maternal care, stress and exposure to toxic compounds (Ansorge et al, 2007).…”