Prepubertal mouse testis growth and maturation and androgen production are acutely sensitive to di-n-butyl phthalate

S Moody; H Goh; A Bielanowicz; P Rippon; K L Loveland; Catherine Itman

doi:10.1210/en.2012-2227

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Prepubertal mouse testis growth and maturation and androgen production are acutely sensitive to di-n-butyl phthalate

Journal article

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Prepubertal mouse testis growth and maturation and androgen production are acutely sensitive to di-n-butyl phthalate

S Moody, H Goh, A Bielanowicz, P Rippon, K L Loveland and Catherine Itman

Endocrinology, Vol.154(9), pp.3460-3475

2013

DOI: https://doi.org/10.1210/en.2012-2227

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Abstract

alpha intermedin

androgen

corn oil

follitropin

inhibin

inhibin A

phthalic acid dibutyl ester

testosterone

transcription factor Sox9

Phthalates are plasticizers with widespread industrial, domestic, and medical applications. Epidemiological data indicating increased incidence of testicular dysgenesis in boys exposed to phthalates in utero are reinforced by studies demonstrating that phthalates impair fetal rodent testis development. Because humans are exposed to phthalates continuously from gestation through adulthood, it is imperative to understand what threat phthalates pose at other life stages. To determine the impact during prepuberty, we assessed the consequences of oral administration of 1 to 500 mg di-n-butyl phthalate (DBP)/kg/d in corn oil to wild-type (C57BL/6J) male mice from 4 to 14 days of age. Dose-dependent effects on testis growth correlated with reduced Sertoli cell proliferation. Histological and immunohistochemical analyses identified delayed spermatogenesis and impaired Sertoli cell maturation after exposure to 10 to 500 mg DBP/kg/d. Interference with the hypothalamic-pituitary-gonadal axis was indicated in mice fed 500 mg DBP/kg/d, which had elevated circulating inhibin but no change in serum FSH. Increased immunohistochemical staining for inhibin-α was apparent at doses of 10 to 500 mg DBP/kg/d. Serum testosterone and testicular androgenactivitywerelower in the 500mgDBP/kg/d group; however, reduced anogenital distance in all DBP-treated mice suggested impaired androgen action at earlier time points. Long-term effects were evident, with smaller anogenital distance and indications of disrupted spermatogenesis in adult mice exposed prepubertally to doses from 1mg DBP/kg/d. These data demonstrate the acute sensitivity of the prepubertal mouse testis to DBP at doses 50- to 500-fold lower than those used in rat and identify the upregulation of inhibin as a potential mechanism of DBP action.

Details

Title: Prepubertal mouse testis growth and maturation and androgen production are acutely sensitive to di-n-butyl phthalate
Authors: S Moody (Author) - Monash University
H Goh (Author) - Monash University
A Bielanowicz (Author) - University of Newcastle
P Rippon (Author) - University of Newcastle
K L Loveland (Author) - Monash University
Catherine Itman (Author) - University of Newcastle
Publication details: Endocrinology, Vol.154(9), pp.3460-3475
Publisher: Endocrine Society
Date published: 2013
DOI: 10.1210/en.2012-2227
ISSN: 0013-7227
Organisation Unit: University of the Sunshine Coast, Queensland
Language: English
Record Identifier: 99449572202621
Output Type: Journal article

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Collaboration types: Domestic collaboration
Web Of Science research areas: Endocrinology & Metabolism

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