Reproductive Endocrine Disruption by Environmental Xenobiotics that Modulate the Estrogen-Signaling Pathway, Particularly Tetrachlorodibenzo-p-dioxin (TCDD)

Abstract

Environmental pollutants are known to exert endocrine-disrupting effects on several hormonal axes of animals, including reproduction and development. Many of these xenobiotics modulate the estrogen-receptor signaling pathway(s) in agonistic or antagonistic ways. Some of the compounds are themselves estrogenic (so-called xenoestrogens, environmental estrogens, or ecoestrogens), and are classified as synthetic estrogens, phyto- or fungal estrogens, alkylphenol ethoxylates; certain non-coplanar polyclorinated biphenyls (PCBs), etc. Other molecules are anti-androgenic, e.g., p, p'-dichloro-diphenyl-dichloroethylene (DDE); while still others disrupt estrogen function in a manner that is dose, species and tissue specific, e.g., certain co-planar PCBs and dioxin-like molecules (e.g., tetrachlorodibenzo-p-dioxin [TCDD]). Exposure to some compounds has been correlated with skewing of sex ratios in aquatic species, and feminization and demasculinization of male animals; declines in human sperm counts; and overall diminution in fertility of birds, fish, and mammals. This review will cover these various xenobiotics and evaluate them for their estrogen-modulating effects; and then further concentrate on TCDD specifically. Dioxins are produced as by-products of herbicide overuse, from paper bleaching, plastics manufacture, and waste incineration. TCDD has been correlated with altered fecundity and endometriosis in monkeys, and with certain cancers in experimental animals and humans. TCDD is also correlated with reproductive deficits in many laboratory species. In summary, we believe that some of the reproductive deficits from endocrine-disrupting xenobiotics may be attributable to the modulation of the estrogen-signaling pathway, in positive and negative manners, depending on dose, species, and tissue specificity.