Perinatal bisphenol A exposure increases estrogen sensitivity of the mammary gland in diverse mouse strains

BACKGROUND: 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-I 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. OBJECTIVES: In the present study we examined whether the mammary glands of CD-1 and C57Bl6 mice exhibited similar responses to 17 beta-estradiol (E-2) and whether perinatal exposure to BPA equally enhanced sensitivity of the mammary glands to E-2 at puberty. METHODS: Immature mice were ovariectomized and treated for 10 days with one of eight doses of E-2. 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 mu g E-2/kg bw/day for 10 days. Morphometric parameters of the mammary gland were compared between strains. RESULTS: Both strains exhibited similar responses to E-2. Perinatal BPA exposure altered responses to E-2 at puberty for several parameters in both strains, although the effect in CD-1 was slightly more pronounced. CONCLUSION: Both mouse strains provide adequate models for the study of perinatal exposure to xenoestrogens.