Epigenetic Transgenerational Actions of Endocrine Disruptors

Evidence that DES has effects in multiple generations have been reported

2006 Study Abstracts

Endocrine disruptors have recently been shown to promote an epigenetic transgenerational phenotype involving a number of disease states (e.g. male infertility). The anti-androgenic fungicide vinclozolin was found to act transiently at the time of embryonic sex determination to promote in the F1 generation a spermatogenic cell defect and subfertility in the male. When the animals were allowed to age up to 1 yr, a number of other disease states developed. This phenotype was transferred through the male germ line to all subsequent generations analyzed (F1–F4). The ability of an environmental factor (i.e. endocrine disruptor) to promote an epigenetic transgenerational phenotype impacts the potential hazards of environmental toxins, mechanisms of disease etiology, and evolutionary biology. The biological importance of the epigenetic actions of environmental agents is reviewed in the context of the primordial germ cell and development of epigenetic transgenerational phenotypes.

Transgenerational Phenomena and Environmental Factors

… Examples of environmental factors during embryonic development that influence the F1 generation include the effects of heavy metals causing cancer, abnormal nutrition that causes diabetic and uterine defects, chemical exposure (i.e. ethosuximide and benzpyrene) causing brain and endocrine defects, and endocrine disruptors such as diethylstilbestrol , phthalates, and dithiothreitol causing reproductive tract and endocrine defects. … Therefore, exposure to a number of environmental factors in utero can cause abnormal phenotypes in the F1 generation in a number of different species. Because the F1 generation is exposed to the environmental factor, the F1 effect is not a transgenerational phenotype.

Transgenerational effects of environmental factors require effects minimally on the F3 generation. This is because the F3 generation is the first generation not directly exposed to the environmental factor. The ability of an external agent to induce a transgenerational phenotype requires a genetic (i.e. DNA sequence) or an epigenetic (i.e. DNA methylation) phenomenon mediated through the germ line . Transgenerational inheritance of an epigenetic state has been shown to occur using several mouse genetic lines and markers and more recently with the use of monozygotic twins with epigenetic differences. … Environmental toxins such as endocrine disruptors have also been shown to influence the F1 generation after parental exposure, but few have demonstrated transgenerational effects on multiple generations. Some evidence that diethylstilbestrol has effects in the F2 generation have been reported.

Endocrine Disruptors and Reproductive Toxicology

… Neonatal exposure to estrogen alters the ER-α and ER-β expression during postnatal testis and hypothalamic/pituitary development Interestingly, neonatal exposure to the estrogenic compound diethylstilbestrol promotes abnormal testis and male reproductive tract development and leads to changes in gene expression. Therefore, actions of estrogenic endocrine disruptors on estrogen receptors may impair normal fetal gonadal development and lead to infertility. …



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