title: A deregulated expression of estrogen-target genes is associated with an altered response to estradiol in aged rats perinatally exposed to bisphenol A.
abstract: Here we assessed the effects of perinatal exposure to bisphenol A (BPA) on the uterine response to 17β-estradiol (E2) in aged rats. Pregnant rats were orally exposed to 0.5 or 50 μg BPA/kg/day from gestational day 9 until weaning. On postnatal day (PND) 360, the rats were ovariectomized and treated with E2 for three months. The uterine tissue of BPA50 and BPA0.5 rats showed increased density of glands with squamous metaplasia (GSM) and glands with daughter glands respectively. Wnt7a expression was lower in GSM of BPA50 rats than in controls. The expression of estrogen receptor 1 (ESR1) and its 5'- untranslated exons ESR1-O and ESR1-OT was lower in BPA50 rats. Both doses of BPA modified the expression of coactivator proteins and epigenetic regulatory enzymes. Thus, perinatal BPA-exposed rats showed different glandular abnormalities associated with deregulated expression of E2-target genes. Different mechanisms would be involved depending on the BPA dose administered.
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: Lucía
authors.initials: L
authors.lastname: Vigezzi
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; Cátedra de Patología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Kass
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: María V
authors.initials: MV
authors.lastname: Tschopp
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: Mónica
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 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; Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina. Electronic address: vlbosqui@fbcb.unl.edu.ar.
authors.forename: Verónica L
authors.initials: VL
authors.lastname: Bosquiazzo
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D017208:Rats, Wistar; D013737:Testis / Q000378:metabolism; D014599:Uterus / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D047628:Estrogen Receptor alpha; D056918:Nuclear Receptor Coactivators; D010636:Phenols; D051153:Wnt Proteins; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; ESR1; Rat; Uterine glands; Uterus; Wnt