The value of mechanistic studies in laboratory animals for the prediction of reproductive effects in wildlife: Endocrine effects on mammalian sexual differentiation

Abstract

AbstractWildlife populations from contaminated ecosystems display a variety of reproductive alterations, including cryptorchidism in the Florida panther, small baculum in young male otters, small penises in alligators, sex reversal in fish, and altered social behavior in birds. The formation of biologically plausible hypotheses regarding disruption of reproduction in wildlife can be facilitated by mechanistic studies on laboratory animals. To this end, we are investigating the in vivo and in vitro effects of endocrine‐disrupting toxicants in rodents. In vitro studies have used receptor binding and transfected cell assays to confirm the suspected mechanism of action, whereas in vivo rodent studies examine altered sexual differentiation. Antiandrogenic pesticides compete with the natural ligands for both rat and human androgen receptors, block androgen‐induced gene expression in vitro and in vivo, delay puberty, reduce sex accessory gland size, and alter male rat sex differentiation. In contrast, xenoestrogens affect female central nervous system sex differentiation and fecundity without producing malformations or infertility in male offspring. Prenatal administration of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) or the TCDD‐like polychlorinated biphenyls produce yet another profile of effects in the offspring, reducing numbers of ejaculated sperm in male progeny and inducing urogenital malformations in females. Although phthalates are reported to be estrogenic in vitro, in vivo exposure causes developmental alterations that more closely resemble antiandrogenic activity. The mammalian data indicate that exposure to endocrine‐disrupting chemicals produces effects that are pathognomonic for mechanisms by which they act. Mechanistic information derived from mammalian studies can enhance our ability to predict toxicant effects on reproduction in fish and wildlife.