Prenatal Exposures of Male Rats to the Environmental Chemicals Bisphenol A and Di(2-Ethylhexyl) Phthalate Impact the Sexual Differentiation Process

• Published in: Endocrinology (Philadelphia) 2015-12, Vol.156 (12), p.4672-4683
• Main Authors: Abdel-Maksoud, Fatma M, Leasor, Khrystyna R, Butzen, Kate, Braden, Timothy D, Akingbemi, Benson T
• Format: Article
• Language: English
• Subjects: Animals; Anti-Mullerian Hormone - metabolism; Benzhydryl Compounds - pharmacology; Bisphenol A; Chemicals; Consumer products; Deoxyribonucleic acid; Diethylhexyl Phthalate - pharmacology; Differentiation; Dioctyl phthalate; DNA; DNA methylation; DNA Methylation - drug effects; DNA methyltransferase; DNA Modification Methylases - drug effects; DNA Modification Methylases - metabolism; Endocrine Disruptors - pharmacology; Environmental Pollutants - pharmacology; Estrogens, Non-Steroidal - pharmacology; Exposure; Female; Follicle Stimulating Hormone, beta Subunit - drug effects; Follicle Stimulating Hormone, beta Subunit - metabolism; GATA4 Transcription Factor - drug effects; GATA4 Transcription Factor - metabolism; Gene expression; Gonadal Dysgenesis; Intrauterine exposure; Luteinizing Hormone, beta Subunit - drug effects; Luteinizing Hormone, beta Subunit - metabolism; Male; Males; Phenols - pharmacology; Phthalates; Pituitary; Pituitary Gland - drug effects; Pituitary Gland - metabolism; Plasticizers - pharmacology; Pregnancy; Prenatal experience; Prenatal Exposure Delayed Effects; Protein expression; Proteins; Rats; Sex differentiation; Sex Differentiation - drug effects; Sex-Determining Region Y Protein - drug effects; Sex-Determining Region Y Protein - metabolism; Steroidogenic factor 1; Steroidogenic Factor 1 - drug effects; Steroidogenic Factor 1 - metabolism; Testes; Testicular Diseases; Testis - drug effects; Testis - metabolism
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2015-1077

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.