Effects of developmental exposure to diethylstilbestrol (DES) in rodents: clues for other environmental estrogens

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Abstract:

The synthetic estrogen diethylstilbestrol (DES) is a potent perinatal endocrine disrupter. In humans and experimental animal models, exposure to DES during critical periods of differentiation permanently alters estrogen target tissues subsequently resulting in structural, functional, and long‐term abnormalities including neoplasia in reproductive tract tissues. Using the developmentally exposed rodent model, multiple mechanisms have been identified that play a role in DES‐induced toxic effects. Although DES is a potent estrogen, it can be used as a model compound to predict the effects of other environmental estrogens. It was, therefore, of particular interest that very low doses of DES were found to adversely affect fertility and increase tumor incidence. These effects were seen at environmentally relevant estrogen dose levels. Not surprising, new studies verify that DES effects are not unique; when other environmental chemicals with estrogenic activity were tested in the experimental rodent model, developmental exposure was shown to result in an increased incidence of neoplasia, including uterine adenocarcinoma, similar to that shown following DES exposure. Finally, a growing number of reports suggest that some adverse effects can be passed on to subsequent generations, although the mechanisms involved in these transgenerational events remain unknown. These data point out the possibility that environmental estrogens and other endocrine disrupting compounds are indeed valid suspects in the alarming rise in adverse reproductive health consequences in human and wildlife populations.

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2001.tb05775.x

Affiliations: Developmental Endocrinology Section, Laboratory of Toxicology, Environmental Toxicology Program, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709

Publication date: July 1, 2001

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