title: Perinatal exposure to bisphenol a increases adult mammary gland progesterone response and cell number.
abstract: Bisphenol A [BPA, 2,2,-bis (hydroxyphenyl) propane] is one of the highest-volume chemicals produced worldwide. It is detected in body fluids of more than 90% of the human population. Originally synthesized as an estrogenic compound, it is currently utilized to manufacture food and beverage containers resulting in uptake with food and drinks. There is concern that exposure to low doses of BPA, defined as less than or equal to 5 mg/kg body weight /d, may have developmental effects on various hormone-responsive organs including the mammary gland. Here, we asked whether perinatal exposure to a range of low doses of BPA is sufficient to alter mammary gland hormone response later on in life, with a possible impact on breast cancer risk. To mimic human exposure, we added BPA to the drinking water of C57/Bl6 breeding pairs. Analysis of the mammary glands of their daughters at puberty showed that estrogen-dependent transcriptional events were perturbed and the number of terminal end buds, estrogen-induced proliferative structures, was altered in a dose-dependent fashion. Importantly, adult females showed an increase in mammary epithelial cell numbers comparable to that seen in females exposed to diethylbestrol, a compound exposure to which was previously linked to increased breast cancer risk. Molecularly, the mRNAs encoding Wnt-4 and receptor activator of nuclear factor κB ligand, two key mediators of hormone function implicated in control of mammary stem cell proliferation and carcinogenesis, showed increased induction by progesterone in the mammary tissue of exposed mice. Thus, perinatal exposure to environmentally relevant doses of BPA alters long-term hormone response that may increase the propensity to develop breast cancer.
authors: ISREC-Swiss Institute for Experimental Cancer Research, National Center of Competence Molecular Oncology, Lausanne, Switzerland.
authors: Ayyakkannu
authors: A
authors: Ayyanan
authors: Ouahiba
authors: O
authors: Laribi
authors: Sonia
authors: S
authors: Schuepbach-Mallepell
authors: Christina
authors: C
authors: Schrick
authors: Maria
authors: M
authors: Gutierrez
authors: Tamara
authors: T
authors: Tanos
authors: Gregory
authors: G
authors: Lefebvre
authors: Jacques
authors: J
authors: Rougemont
authors: Ozden
authors: O
authors: Yalcin-Ozuysal
authors: Cathrin
authors: C
authors: Brisken
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D001943:Breast Neoplasms; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000494:pharmacology*; D053245:RANK Ligand / Q000235:genetics; D060528:Wnt4 Protein / Q000235:genetics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; D011374:Progesterone; D053245:RANK Ligand; D060528:Wnt4 Protein; C006780:bisphenol A; D000098826:Bisphenol A Compounds