期刊
ENVIRONMENTAL HEALTH PERSPECTIVES
卷 117, 期 4, 页码 515-521出版社
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.11870
关键词
androgens; anti-Mullerian hormone; endocrine disruption; explant culture; fetal testis; gonocytes; phthalates
资金
- INSERM (Institut National de la Sante et de la Recherche Medicale)
- Ministere de l'Enseignement Superieur et de la Recherche
- European Union [QLK-CT-200-00603, 212844]
- European Council
- PLAST-IMPACT [ANR-06-PNRA-008-05]
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-ethythexyl) 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-Mullerian 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.
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