Antenatal sex-hormone exposure induces lesions in mouse reproductive organs, which are similar to those in humans exposed in utero to a synthetic estrogen, diethylstilbestrol. The developing organisms including rodents, fish and amphibians are particularly sensitive to exposure to estrogenic chemicals during a critical window. Exposure to estrogens during the critical period induces long-term changes in reproductive as well as nonreproductive organs, including persistent molecular alterations. The antenatal mouse model can be utilized as an indicator of possible long-term consequences of exposure to exogenous estrogenic compounds including possible environmental endocrine disruptors. Many chemicals released into the environment potentially disrupt the endocrine system in wildlife and humans, some of which exhibit estrogenic activity by binding to the estrogen receptors. Estrogen responsive genes, therefore, need to be identified to understand the molecular basis of estrogenic actions. In order to understand molecular mechanisms of estrogenic chemicals on developing organisms, we are identifying estrogen responsive genes using cDNA microarray, quantitative RT-PCR, and differential display methods, and genes related to the estrogen-independent vaginal changes in mice induced by estrogens during the critical window. In this review, discussion of our own findings related to endocrine distuptor issue will be provided.Key words: BPA, bisphenol-A; DES, diethylstilbestrol; Ez, 17P-estradiol; ER, estrogen receptor; P, progesterone; PR, progesterone receptor; T, testosterone; TP, testosterone propionate
ANTENATAL EFFECTS OF ESTROGENS
IN DEVELOPING MICEAntenatal exposure of estrogens, including natural, synthetic and phytoestrogens, have been found to induce lesions in the female mouse reproductive tracts, and the possible relevance of the mouse findings to the development of cancer in humans was emphasized (Takasugi, 1976; Forsberg, 1979; Herbst and Bern, 1981 ;Takasugi and Bern, 1988; Bern, 1996; McLachlan and Newbold, 1996). Herbst et al.(1 981) demonstrated a close correlation between the Occurrence of vaginal clear cell adenocarcinoma in young women and early intrauterine exposure to a synthetic estrogen, diethylstilbestrol (DES), in the early 1970s. Many chemicals released into the environment potentially disrupt the endocrine system in wildlife and humans, some of which have estrogenic activity as determined by binding to the estrogen receptors (ERs) (Colborn and Clement, 1992). Mice exposed antenatally to estrogens provide a model for exploration of the consequences of DES exposure in the human, because mouse genital tract development at birth is similar to that of the human fetus at the end of the first trimester. The neonatal mouse model has been utilized to demonstrate the long-term effects of early sex hormone exposure on the female reproductive tract
