title: Prenatal Exposures of Male Rats to the Environmental Chemicals Bisphenol A and Di(2-Ethylhexyl) Phthalate Impact the Sexual Differentiation Process.
abstract: The increasing incidence of reproductive anomalies, described as testicular dysgenesis syndrome, is thought to be related to the exposure of the population to chemicals in the environment. Bisphenol A (BPA) and di(2-ethylhexyl)phthalate (DEHP), which have hormonal and antihormonal activity, have attracted public attention due to their presence in consumer products. The present study investigated the effects of BPA and DEHP on reproductive development. Timed-pregnant female rats were exposed to BPA and DEHP by gavage from gestational days 12 to 21. Results showed that prenatal exposures to test chemicals exerted variable effects on steroidogenic factor 1 and GATA binding protein 4 protein expression and increased (P < .05) sex-determining region Y-box 9 and antimüllerian hormone protein in the infantile rat testis compared with levels in the control unexposed animals. Pituitary LHβ and FSHβ subunit protein expression was increased (P < .05) in BPA- and DEHP-exposed prepubertal male rats but were decreased (P < .05) in adult animals relative to control. Exposure to both BPA and DEHP in utero inhibited (P < .05) global DNA hydroxymethylation in the adult testis in association with altered DNA methyltransferase protein expression. Together the present data suggest that altered developmental programming in the testes associated with chemical exposures are related to the disruption of sexual differentiation events and DNA methylation patterns. The chemical-induced effects impact the development of steroidogenic capacity in the adult testis.
authors.affiliation: Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn, Auburn University, Alabama 36849.
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Abdel-Maksoud
authors.affiliation: Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn, Auburn University, Alabama 36849.
authors.forename: Khrystyna R
authors.initials: KR
authors.lastname: Leasor
authors.affiliation: Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn, Auburn University, Alabama 36849.
authors.forename: Kate
authors.initials: K
authors.lastname: Butzen
authors.affiliation: Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn, Auburn University, Alabama 36849.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Braden
authors.affiliation: Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn, Auburn University, Alabama 36849.
authors.forename: Benson T
authors.initials: BT
authors.lastname: Akingbemi
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000187:drug effects / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D052244:Endocrine Disruptors / Q000494:pharmacology; D004785:Environmental Pollutants / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000187:drug effects / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D006059:Gonadal Dysgenesis; D037101:Luteinizing Hormone, beta Subunit / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010968:Plasticizers / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012733:Sex Differentiation / Q000187:drug effects*; D051876:Sex-Determining Region Y Protein / Q000187:drug effects / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000187:drug effects / Q000378:metabolism; D013733:Testicular Diseases; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D054304:Anti-Mullerian Hormone; D001559:Benzhydryl Compounds; D015254:DNA Modification Methylases; D004051:Diethylhexyl Phthalate; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D037201:Follicle Stimulating Hormone, beta Subunit; D050991:GATA4 Transcription Factor; D037101:Luteinizing Hormone, beta Subunit; D010636:Phenols; D010968:Plasticizers; D051876:Sex-Determining Region Y Protein; D054339:Steroidogenic Factor 1; C084365:Gata4 protein, rat; C515060:steroidogenic factor 1, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds