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Prenatal exposure to an environmentally relevant phthalate mixture disrupts testicular steroidogenesis in adult male mice.

ABSTRACT: Endocrine disrupting chemicals (EDCs) in the environment are considered to be a contributing factor to the decline in the sperm quality. With growing evidence of the harmful effects of EDCs on the male reproductive system, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects reproductive outcomes and androgen synthesis. In this study, an environmentally relevant composition of phthalates (15% DiNP, 21% DEHP, 36% DEP, 15% DBP, 8% DiBP, and 5% BBzP) that were detected in urine samples of pregnant women in Illinois, United States, was used. Pregnant CD-1 mice (F0) were orally dosed with a vehicle or the phthalate mixtures (20?µg/kg/day, 200?µg/kg/day, 200?mg/kg/day, or 500?mg/kg/day) from gestational day 10.5 to the day of birth. Then, the indices of the reproductive function of the F1 males born to these dams were assessed. Those male mice prenatally exposed to the phthalate mixture had smaller gonads, prostates and seminal vesicles, especially in the 20?µg/kg/day and 500?mg/kg/day phthalate mixture groups, compared to the controls. Importantly, at the age of 12 months, those prenatally exposed mice had significantly lower serum testosterone concentrations accompanied by the decreased mRNA expression of testicular steroidogenic genes (StAR, Cyp11, and Cyp17) and impaired spermatogenesis. Taken together, this study found that prenatal exposure to environmentally relevant doses of a phthalate mixture caused a life-long impact on the reproduction in male mice.

SUBMITTER: Barakat R

PROVIDER: S-EPMC6511329 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Prenatal exposure to an environmentally relevant phthalate mixture disrupts testicular steroidogenesis in adult male mice.

Barakat Radwa R Seymore Talia T Lin Po-Ching Patrick PP Park Chan Jin CJ Ko CheMyong Jay CJ

Environmental research 20190213

Endocrine disrupting chemicals (EDCs) in the environment are considered to be a contributing factor to the decline in the sperm quality. With growing evidence of the harmful effects of EDCs on the male reproductive system, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects reproductive outcomes and androgen synthesis. In this study, an environmentally relevant composition of phthalates (15% DiNP, 21% DEHP, 36% DEP, 15% DBP, 8% DiBP, ...[more]

PMID: 30802670

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Project description:BackgroundWe have previously shown that chronic exposure of adult male mice to low doses of di(2-ethylhexyl) phthalate (DEHP) altered male sexual behavior and induced down-regulation of the androgen receptor (AR) in the neural circuitry controlling this behavior.ObjectivesThe cellular mechanisms induced by chronic exposure of adult male mice to low doses of DEHP alone or in an environmental phthalate mixture were studied.MethodsTwo-month-old C57BL/6J males were exposed orally for 8 wk to DEHP alone (0, 5, or 50μg/kg/d) or to DEHP (50μg/kg/d) in a phthalate mixture. Behavior, dendritic density per 50-μm length, pre-/postsynaptic markers, synapse ultrastructure, and bioenergetic activity were analyzed.ResultsMice exposed to DEHP either alone or in a phthalate mixture differed in mating, emission of ultrasonic vocalizations, and the ability to attract receptive females in urinary preference tests from control mice. Analyses in the medial preoptic area, the key hypothalamic region involved in male sexual behavior, showed lower dendritic spine density and protein levels of glutamate receptors and differences in other postsynaptic components and presynaptic markers between the treated groups. Ultrastructural observation of dendritic synapses by electron microscopy showed comparable morphology between the treated groups. Metabolic analyses highlighted differences in hypothalamic metabolites of males exposed to DEHP alone or in a phthalate mixture compared to control mice. These differences included lower tryptophan and higher NAD+ levels, respectively, a precursor and end product of the kynurenine pathway of tryptophan metabolism. The protein amounts of the xenobiotic aryl hydrocarbon receptor, one of the targets of this metabolic pathway and known negative regulator of the AR, were higher in the medial preoptic area of exposed male mice.DiscussionDifferences in behavior of male mice exposed to environmental doses of phthalates were associated with differences in neural structure and metabolism, with possibly a key role of the kynurenine pathway of tryptophan metabolism in the effects mediated by these substances. https://doi.org/10.1289/EHP11514.

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Prenatal exposure to an environmentally relevant phthalate mixture disrupts testicular steroidogenesis in adult male mice.

Publications

Prenatal exposure to an environmentally relevant phthalate mixture disrupts testicular steroidogenesis in adult male mice.

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