Perinatal exposure to bisphenol A modifies the transcriptional regulation of the β-Casein gene during secretory activation of the rat mammary gland. (5th January 2017)

• Record Type: Journal Article
• Authors: Altamirano, Gabriela A.; Ramos, Jorge G.; Gomez, Ayelen L.; Luque, Enrique H.; Muñoz-de-Toro, Monica; Kass, Laura
• Is Part Of: Molecular and cellular endocrinology. Volume 439(2017)
• Page Start: 407
• Page End: 418
• Publication Date: 2017-01-05
• Subjects: Bisphenol A -- Mammary gland differentiation -- β-Casein -- Epigenetic modifications -- Lactation; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.09.032
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: Perinatal BPA exposure decreased β-Cas gene expression independently of PRL signaling. BPA altered the expression of HDAC1, HDAC3 and EZH2 in the lactating mammary gland. BPA induced acetylation and methylation of histones in the β-Cas gene. BPA induced changes in the DNA methylation status of the β-Cas gene.