Cellular and molecular effects of developmental exposure to DES: implications for other environmental estrogens

1995 Study Abstract

Concerns have been raised regarding the role of environmental and dietary estrogens as possible contributors to an increased incidence of various abnormalities in estrogen-target tissues of both sexes. These abnormalities include breast cancer, endometriosis, fibroids, and uterine adenocarcinoma in females, as well as alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems in males. Whether these concerns are valid remains to be determined; however, studies with the potent synthetic estrogen diethylstilbestrol (DES) suggest that exogenous estrogen exposure during critical stages of development can result in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES has potent estrogenic activity, it may be used as a model compound to study the effects of weaker environmental estrogens, many of which may fit into the category of endocrine disruptors.

Conclusions

There are many possible cellular and molecular mechanisms that may be involved in the toxic response to DES and other environmental estrogens if an organism is exposed during critical stages of development. Several mechanisms have been discussed in this report. Studies with the developmentally DES-exposed murine model have duplicated and predicted many of the lesions seen in similarly DES-exposed humans and in the wildlife population. Currently, there is increased interest in the effects of other environmental estrogens and antiandrogens on reproductive tract differentiation and development. Whether these compounds have effects similar to DES is uncertain, but since low doses of DES demonstrate alterations in both male and female exposed offspring, the possibility of adverse effects from other compounds with estrogenic and/or antiandrogenic activity must be considered.

Sources and Full Study

• Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens, Newbold R, Environ Health Perspect. 1995 Oct;103 Suppl 7:83-7. PMID: 8593881.
• Full study, Environ Health Perspect. 1995 Oct; 103(Suppl 7): 83–87, PMC1518878, 1995 Oct.

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