MATERNAL GENISTEIN EXPOSURE MIMICS THE EFFECTS OF ESTROGEN ON MAMMARY-GLAND DEVELOPMENT IN FEMALE MOUSE OFFSPRING

Human and animal data indicate that a high maternal estrogen exposure during pregnancy increases breast cancer risk among daughters. This ma y reflect an increase in the epithelial structures that are the sites for malignant transformation, i.e., terminal end buds (TEBs), and a re duction in epithelial differentiation in the mammary gland. Some phyto estrogens, such as genistein which is a major component in soy-based f oods, and zearalenone, a mycotoxin found in agricultural products, hav e estrogenic effects on the reproductive system, breast and brain. The present study examined whether in utero exposure to genistein or zear alenone influences mammary gland development. Pregnant mice were injec ted daily with i) 20 ng estradiol (E2); ii) 20 mu g genistein; iii) 2 mu g zearalenone; iv) 2 mu g tamoxifen (TAM), a partial estrogen recep tor agonist; or v) oil-vehicle between days 15 and 20 of gestation. E2 , genistein, zearalenone, and tamoxifen all increased the density of T EBs in the mammary glands. Genistein reduced, and zearalenone increase d, epithelial differentiation. Zearalenone also increased epithelial d ensity, when compared with the vehicle-controls. None of the treatment s had permanent effects on circulating E2 levels. Maternal exposure to E2 accelerated body weight gain, physical maturation (eyelid opening) , and puberty onset (vaginal opening) in the female offspring. Geniste in and tamoxifen had similar effects on puberty onset than E2. Zearale none caused persistent cornification of the estrus smears. These findi ngs indicate that maternal exposure to physiological doses of genistei n mimics the effects of E2 on the mammary gland and reproductive syste ms in the offspring. Thus, our results suggest that genistein acts as an estrogen in utero, and may increase the incidence of mammary tumors if given through a pregnant mother. The estrogenic effects of zearale none on the mammary gland, in contrast, are probably counteracted by t he permanent changes in estrus cycling.