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Endocrinology ; 156(12): 4672-83, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26372177

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 LHß and FSHß 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.


Subject(s)
Benzhydryl Compounds/pharmacology , Diethylhexyl Phthalate/pharmacology , Environmental Pollutants/pharmacology , Estrogens, Non-Steroidal/pharmacology , Phenols/pharmacology , Plasticizers/pharmacology , Sex Differentiation/drug effects , Testis/drug effects , Animals , Anti-Mullerian Hormone/metabolism , DNA Methylation/drug effects , DNA Modification Methylases/drug effects , DNA Modification Methylases/metabolism , Endocrine Disruptors/pharmacology , Female , Follicle Stimulating Hormone, beta Subunit/drug effects , Follicle Stimulating Hormone, beta Subunit/metabolism , GATA4 Transcription Factor/drug effects , GATA4 Transcription Factor/metabolism , Gonadal Dysgenesis , Luteinizing Hormone, beta Subunit/drug effects , Luteinizing Hormone, beta Subunit/metabolism , Male , Pituitary Gland/drug effects , Pituitary Gland/metabolism , Pregnancy , Prenatal Exposure Delayed Effects , Rats , Sex-Determining Region Y Protein/drug effects , Sex-Determining Region Y Protein/metabolism , Steroidogenic Factor 1/drug effects , Steroidogenic Factor 1/metabolism , Testicular Diseases , Testis/metabolism
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