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

Abstract

BackgroundStudies 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.ObjectivesIn 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.MethodsImmature 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.ResultsBoth 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.ConclusionBoth mouse strains provide adequate models for the study of perinatal exposure to xenoestrogens.

Low dose effects of bisphenol A

“…Mammary gland Since 2007, 11 studies, including one examining the nonhuman primate, 129 have examined the effects of developmental exposures to BPA on the morphology of the mammary gland [130][131][132][133][134][135][136] and altered responses of this organ to carcinogenic challenges. [137][138][139] Another recent study revealed the presence of carcinomas in the mammary glands of rats exposed to low doses of BPA only during early development in the absence of any additional carcinogen treatment, providing further evidence that the mammary gland is affected by BPA.…”

Impact of Environmental Contaminants on Breast Cancer / Wpływ Zanieczyszczenia Środowiska Na Raka Piersi

“…Thus, perinatal exposure to environmentally relevant doses of BPA alters long-term hormone response that may increase the propensity to develop breast cancer [125]. In mice, perinatal exposure to environmentally relevant BPA levels induced alterations of the mammary gland architecture which manifested during fetal morphogenesis [126][127][128][129] and throughout life, including the development of pre-neoplastic lesions, while in rats gestational exposure to BPA induced pre-neoplastic lesions and carcinoma in situ that manifested in adulthood in the absence of any additional treatment [130]. In rats high-dose BPA exposure induced changes in genes related to differentiation suggesting alterations in the normal development of the gland.…”

Gender and Age Related Modulation of Xenoestrogen-Induced Tumorigenesis

“…Transplacental exposure to xenoestrogens enhanced responses to estrogen in the mammary tissue of pubertal mice [83]; it could be suggested that xenoestrogen exposure during puberty might also provide a further input to the carcinogenesis process in breast tissue where early programming was already altered. Most important, puberty itself represents a specific susceptible window.…”