Prenatal exposure to bisphenol A promotes angiogenesis and alters steroid-mediated responses in the mammary glands of cycling rats

Abstract

Prenatal exposure to BPA disturbs mammary gland histoarchitecture and increases thecarcinogenic susceptibility to chemical challenges administered long after BPA exposure.Our aim was to assess the effect of prenatal BPA exposure on mammary glandangiogenesis and steroid hormone pathways in virgin cycling rats. Pregnant Wistar ratswere exposed to either 25 or 250 μg/kg/day (25 and 250 BPA, respectively) or to vehicle.Female offspring were autopsied on postnatal day (PND) 50 or 110. Ovarian steroid serumlevels, the expression of steroid receptors and their co-regulators SRC-3 and SMRT in themammary gland, and angiogenesis were evaluated. At PND 50, all BPA-treated animalshad lower serum levels of progesterone, while estradiol levels remained unchanged. Thehigher dose of BPA increased mammary ERa and decreased SRC-3 expression at PND 50and PND 110. SMRT protein levels were similar among groups at PND 50, whereas atPND 110, animals exposed to 250 BPA showed a lower SMRT expression. Interestingly, inthe control and 25 BPA groups, SMRT increased from PND 50 to PND 110. At PND 50, anincreased vascular area associated with higher VEGF expression was observed in the 250BPA-treated rats. At PND 110, the vascular area was still increased, but VEGF expressionwas similar to that of control rats. The present results demonstrate that prenatal exposure toBPA alters the endocrine environment of the mammary gland and its angiogenic process.Increased angiogenesis and altered steroid hormone signals could explain the higherfrequency of pre-neoplastic lesions found later in life.