Perinatal Bisphenol A Exposure Increases Estrogen Sensitivity of the Mammary Gland in Diverse Mouse Strains

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Abstract
Studies of low-dose effects of xenoestrogens have yielded conflicting results that may be attributed to differences in estrogen sensitivity between the rodent strains examined. Perinatal exposure of CD-1 mice to low doses of the xenoestrogen bisphenol A (BPA) alters peripubertal mammary gland development. Future studies to assess the role of estrogen receptors as mediators of BPA action require estrogen receptor knock-out mice that were generated on a C57Bl6 background. The sensitivity of the C57Bl6 strain to estradiol and BPA is unknown. In the present study we examined whether the mammary glands of CD-1 and C57Bl6 mice exhibited similar responses to 17β-estradiol (E2) and whether perinatal exposure to BPA equally enhanced sensitivity of the mammary glands to E2 at puberty. Immature mice were ovariectomized and treated for 10 days with one of eight doses of E2. Morphological mammary gland parameters were examined to identify doses producing half-maximal effects. Mice were exposed perinatally to 0 or 250 ng BPA/kg body weight (bw)/day from gestational day 8 until postnatal day (PND) 2. On PND25, female offspring were ovariectomized and given an estrogen challenge of 0, 0.5, or 1 μg E2/kg bw/day for 10 days. Morphometric parameters of the mammary gland were compared between strains. Both strains exhibited similar responses to E2. Perinatal BPA exposure altered responses to E2 at puberty for several parameters in both strains, although the effect in CD-1 was slightly more pronounced. Both mouse strains provide adequate models for the study of perinatal exposure to xenoestrogens.