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Environ Health Perspect. 2009 Apr;117(4):515-21. doi: 10.1289/ehp.11870. Epub 2008 Dec 1.

Time- and dose-related effects of di-(2-ethylhexyl) phthalate and its main metabolites on the function of the rat fetal testis in vitro.

Author information

1
INSERM (Institut National de la Santé et de la Recherche Médicale), U625, GERHM, Université Rennes I, Campus de Beaulieu, Rennes, Bretagne, France.

Abstract

BACKGROUND:

Endocrine-disrupting effects of phthalates are understood primarily from in utero exposures within the fetal rat testis. Nevertheless, their path of action, dose-response character, and cellular target(s) within the fetal testis are not known.

OBJECTIVES:

In this study we investigated the effects of di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP), and several of their metabolites on the development of organo-cultured testes from rat fetus.

METHODS:

We removed testes from 14.5-day-old rat fetuses and cultured them for 1-3 days with or without DEHP, MEHP, and the metabolites.

RESULTS:

DEHP (10(-5) M) produced a proandrogenic effect after 3 days of culture, whereas MEHP disrupted testis morphology and function. Leydig cells were the first affected by MEHP, with a number of them being inappropriately located within some seminiferous tubules. Additionally, we found a time- and dose-dependent reduction of testosterone. By 48 hr, gonocyte proliferation had decreased, whereas apoptosis increased. Sertoli cell number was unaffected, although some cells appeared vacuolated, and production of anti-Müllerian hormone decreased in a time- and dose-dependent manner. The derived metabolite mono-(2-ethyl-5-hydroxyhexyl) phthalate was the only one to cause deleterious effects to the rat fetal testis in vitro.

CONCLUSION:

We hope that this in vitro method will facilitate the study of different phthalate esters and other endocrine disruptors for direct testicular effects.

KEYWORDS:

androgens; anti-Müllerian hormone; endocrine disruption; explant culture; fetal testis; gonocytes; phthalates

PMID:
19440488
PMCID:
PMC2679593
DOI:
10.1289/ehp.11870
[Indexed for MEDLINE]
Free PMC Article

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