Chauvigné François, Menuet Arnaud, Lesné Laurianne, Chagnon Marie-Christine, Chevrier Cécile, Regnier Jean-François, Angerer Jürgen, Jégou Bernard
INSERM (Institut National de la Santé et de la Recherche Médicale), U625, GERHM, Université Rennes I, Campus de Beaulieu, Rennes, Bretagne, France.
Environ Health Perspect. 2009 Apr;117(4):515-21. doi: 10.1289/ehp.11870. Epub 2008 Dec 1.
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.
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.
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.
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.
We hope that this in vitro method will facilitate the study of different phthalate esters and other endocrine disruptors for direct testicular effects.
邻苯二甲酸酯的内分泌干扰作用主要是从大鼠胎儿睾丸的子宫内暴露情况了解到的。然而，它们在胎儿睾丸内的作用途径、剂量反应特征和细胞靶点尚不清楚。
在本研究中，我们调查了邻苯二甲酸二（2-乙基己基）酯（DEHP）、邻苯二甲酸单（2-乙基己基）酯（MEHP）及其几种代谢产物对大鼠胎儿器官培养睾丸发育的影响。
我们从14.5日龄的大鼠胎儿中取出睾丸，并在有或没有DEHP、MEHP和代谢产物的情况下培养1-3天。
培养3天后，DEHP（10⁻⁵ M）产生了促雄激素作用，而MEHP破坏了睾丸的形态和功能。间质细胞是受MEHP影响的第一类细胞，其中一些细胞在一些生精小管内的位置不当。此外，我们发现睾酮水平呈时间和剂量依赖性降低。到48小时时，生殖母细胞增殖减少，而凋亡增加。支持细胞数量未受影响，尽管一些细胞出现空泡化，抗苗勒管激素的产生呈时间和剂量依赖性降低。衍生代谢产物邻苯二甲酸单（2-乙基-5-羟基己基）酯是唯一在体外对大鼠胎儿睾丸产生有害影响的物质。
我们希望这种体外方法将有助于研究不同的邻苯二甲酸酯和其他内分泌干扰物对睾丸的直接影响。
