Perinatal Exposure to Bisphenol A Increases Adult Mammary Gland Progesterone Response and Cell Number

Autor: Maria Gutierrez, Ayyakkannu Ayyanan, Gregory Lefebvre, Sonia Schuepbach-Mallepell, Jacques Rougemont, Ozden Yalcin-Ozuysal, Christina Schrick, Cathrin Brisken, Tamara Tanos, Ouahiba Laribi
Přispěvatelé: TR103812, Yalçın Özuysal, Özden, Izmir Institute of Technology. Molecular Biology and Genetics
Rok vydání: 2011
Předmět:
Male
Proliferation
Mammary gland
Diethylstilbestrol
Mice
Breast cancer
Bisphenol A
Sensitivity
Endocrinology
Pregnancy
Wnt4 Protein
Mechanisms
Mouse Strains
Progesterone
Original Research
education.field_of_study
Perinatal Exposure
General Medicine
Estrogen-Receptor-Alpha
medicine.anatomical_structure
Prenatal Exposure Delayed Effects
Female
Wnt4 protein
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Risk
endocrine system
medicine.medical_specialty
medicine.drug_class
Population
Breast Neoplasms
Biology
Amphiregulin
NURSA Molecule Pages: Nuclear Receptors: PR
Mammary Glands
Animal
Phenols
Internal medicine
medicine
Animals
Women
Breast-Cancer
Benzhydryl Compounds
education
Molecular Biology
Body fluid
RANK ligand
RANK Ligand
Epithelial Cells
Ligands: Bisphenol A
Estrogen
Hormone
Zdroj: Molecular Endocrinology. 25:1915-1923
ISSN: 1944-9917
0888-8809
Popis: 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 kB 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. © 2011 by The Endocrine Society.
Swiss Science Foundation (NRP50); Swiss Federal Public Health Office
Databáze: OpenAIRE
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