title: 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 the carcinogenic susceptibility to chemical challenges administered long after BPA exposure. Our aim was to assess the effect of prenatal BPA exposure on mammary gland angiogenesis and steroid hormone pathways in virgin cycling rats. Pregnant Wistar rats were exposed to either 25 or 250 g/kg/day (25 and 250 BPA, respectively) or to vehicle. Female offspring were autopsied on postnatal day (PND) 50 or 110. Ovarian steroid serum levels, the expression of steroid receptors and their co-regulators SRC-3 and SMRT in the mammary gland, and angiogenesis were evaluated. At PND 50, all BPA-treated animals had lower serum levels of progesterone, while estradiol levels remained unchanged. The higher dose of BPA increased mammary ERα and decreased SRC-3 expression at PND 50 and PND 110. SMRT protein levels were similar among groups at PND 50, whereas at PND 110, animals exposed to 250 BPA showed a lower SMRT expression. Interestingly, in the control and 25 BPA groups, SMRT increased from PND 50 to PND 110. At PND 50, an increased vascular area associated with higher VEGF expression was observed in the 250 BPA-treated rats. At PND 110, the vascular area was still increased, but VEGF expression was similar to that of control rats. The present results demonstrate that prenatal exposure to BPA alters the endocrine environment of the mammary gland and its angiogenic process. Increased angiogenesis and altered steroid hormone signals could explain the higher frequency of pre-neoplastic lesions found later in life. This article is part of a Special Issue entitled 'Endocrine disruptors'.
authors.affiliation: Laboratorio de Endocrinología y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Universidad Nacional del Litoral (UNL), Santa Fe, Argentina.
authors.forename: Milena
authors.initials: M
authors.lastname: Durando
authors.forename: Laura
authors.initials: L
authors.lastname: Kass
authors.forename: Virginia
authors.initials: V
authors.lastname: Perdomo
authors.forename: Verónica L
authors.initials: VL
authors.lastname: Bosquiazzo
authors.forename: Enrique H
authors.initials: EH
authors.lastname: Luque
authors.forename: Mónica
authors.initials: M
authors.lastname: Muñoz-de-Toro
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D005260:Female; D008321:Mammary Glands, Animal / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010636:Phenols / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D055765:Shc Signaling Adaptor Proteins / Q000096:biosynthesis; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D047628:Estrogen Receptor alpha; D010636:Phenols; D011374:Progesterone; D055765:Shc Signaling Adaptor Proteins; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; C485683:Shc3 protein, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds