Effects of Perinatal Estrogen Exposure on Fertility and Cancer in Mice

Retha R. Newbold

Developmental Endocrinology Section, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA E-mail: newbo [email protected]

Concerns have been raised regarding the reproductive and health hazards of chemicals in the environment that have potential endocrine disrupting effects. These concerns include increased incidences of breast, ovarian, and uterine cancer, endometriosis, fibroids, infertility, and early menopause in women; in men, alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems have been suggested. Studies with the potent synthetic estrogen diethyl-stilbestrol (DES) have shown that exogenous estrogen exposure during critical stages of development results 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 is a potent environmental estrogen, studying its effects at low dose levels in an experimental animal model offers a unique opportunity to identify adverse effects that may be caused by weaker environmental estrogens which fit the category of endocrine disruptors.

Keywords. Diethylstilbestrol, DES, Estrogenic, Estrogen, Estrogen receptor, Embryogenesis, Perinatal exposure, Reproductive tract development, Genital tract, Sex hormones, Sex differentiation, Infertility

1 Introduction 172

2 Prenatal DES Exposure as an Example 173

3 Effects on Males 174

3.1 Fertility 175

3.2 Cancer 175

4 Effects on Females 176

4.1 Fertility 177

4.2 Cancer 178

5 Mechanisms of Reproductive Tract Toxicity 180

6 Multigenerational Effects 181

7 Not Just DES - Other Examples 182

8 Summary and Conclusions 184

9 References 185

The Handbook of Environmental Chemistry Vol. 3, Part M Endocrine Disruptors, Part II (ed. by M. Metzler)

© Springer-Verlag Berlin Heidelberg 2002

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