Time- and Dose-Related Effects of Di-(2-ethylhexyl) Phthalate and Its Main Metabolites on the Function of the Rat Fetal Testis in Vitro
نویسندگان
چکیده
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.
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Chronic Effects of Di(2-ethylhexyl)phthalate on Stereological Parameters of Testis in Adult Wistar Rats
Objective(s) In recent years concerns have been raised regarding the incidence of male reproductive disorders from exposure to endocrine disruptors. So, chronic effects of di(2-ethylhexyl)phthalate were studied on histological and stereological structure of testis in adult Wistar rats. Materials and Methods Thirty two adult Wistar rats were randomly divided in four equal experiment groups; o...
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