title: Perinatal exposure to bisphenol A modifies the transcriptional regulation of the β-Casein gene during secretory activation of the rat mammary gland.
abstract: With the aim to analyze whether bisphenol A (BPA) modifies β-Casein (β-Cas) synthesis and transcriptional regulation in perinatally exposed animals, here, pregnant F0 rats were orally exposed to 0, 0.6 or 52 μg BPA/kg/day from gestation day 9 until weaning. Then, F1 females were bred and mammary glands were obtained on lactation day 2. Perinatal BPA exposure decreased β-Cas expression without modifying the activation of prolactin receptor. It also decreased the expression of glucocorticoid receptor in BPA52-exposed dams and β1 and α6 integrins as well as dystroglycan in both BPA groups. In addition, BPA exposure altered the expression of histone-modifying enzymes and induced histone modifications and DNA methylation in the promoter, enhancer and exon VII of the β-Cas gene. An impaired crosstalk between the extracellular matrix and lactogenic hormone signaling pathways and epigenetic modifications of the β-Cas gene could be the molecular mechanisms by which BPA decreased β-Cas expression.
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Cátedra de Patología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Altamirano
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Ramos
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Ayelen L
authors.initials: AL
authors.lastname: Gomez
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Cátedra de Fisiología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Enrique H
authors.initials: EH
authors.lastname: Luque
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Cátedra de Patología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Monica
authors.initials: M
authors.lastname: Muñoz-de-Toro
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Cátedra de Patología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina. Electronic address: lkass@fbcb.unl.edu.ar.
authors.forename: Laura
authors.initials: L
authors.lastname: Kass
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002364:Caseins / Q000235:genetics* / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D019175:DNA Methylation / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D007774:Lactation / Q000235:genetics; D007797:Laminin / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002364:Caseins; D006657:Histones; D007797:Laminin; D010636:Phenols; D011965:Receptors, Glucocorticoid; D017474:Receptors, Laminin; D011981:Receptors, Prolactin; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Epigenetic modifications; Lactation; Mammary gland differentiation; β-Casein