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This Article Full Text Full Text (PDF) All Versions of this Article: 72/6/1344    most recent biolreprod.104.036301v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Markey, C. M. Articles by Soto, A. M. Search for Related Content PubMed PubMed Citation Articles by Markey, C. M. Articles by Soto, A. M. Agricola Articles by Markey, C. M. Articles by Soto, A. M.

Long-Term Effects of Fetal Exposure to Low Doses of the Xenoestrogen Bisphenol-A in the Female Mouse Genital Tract¹

Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111-1800

Developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. Humans are routinely exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials and plastic food and beverage containers. The aim of the present study was to determine the effects of in utero exposure to low, environmentally relevant doses of BPA on the development of female reproductive tissues in CD-1 mice. In previous publications, we have shown that this treatment alters the morphology of the mammary gland and affects estrous cyclicity. Here we report that in utero exposure to 25 and 250 ng BPA/ kg of body weight per day via osmotic pumps implanted into pregnant dams at Gestational Day 9 induces alterations in the genital tract of female offspring that are revealed during adulthood. They include decreased wet weight of the vagina, decreased volume of the endometrial lamina propria, increased incorporation of bromodeoxyuridine into the DNA of endometrial gland epithelial cells, and increased expression of estrogen receptor- (ER) and progesterone receptor in the luminal epithelium of the endometrium and subepithelial stroma. Because ER is known to be expressed in these estrogen-target organs at the time of BPA exposure, it is plausible that BPA may directly affect the expression of ER-controlled genes involved in the morphogenesis of these organs. In addition, BPA-induced alterations that specifically affect hypothalamic-pituitary-gonadal axis function may further contribute to the anomalies observed at 3 mo of age, long after the cessation of BPA exposure.

early development, environment, estradiol receptor, progesterone receptor, toxicology

² Correspondence: Ana M. Soto, Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111-1800. FAX: 617 636 3971; ana.soto{at}tufts.edu

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