Phthalates impair germ cell development in the human fetal testis in vitro without change in testosterone production.
Phthalates impair germ cell development in the human fetal testis in vitro without change in testosterone production.
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DOI：
10.1289/ehp.11146
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发表时间：
2009-01
影响因子：
10.4
通讯作者：
Rouiller-Fabre V
中科院分区：
文献类型：
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作者：
Lambrot R;Muczynski V;Lécureuil C;Angenard G;Coffigny H;Pairault C;Moison D;Frydman R;Habert R;Rouiller-Fabre V
几项研究已经描述了男性生殖障碍的频率越来越高，这些疾病可能在胎儿生活中有共同的起源，并被假设由内分泌干扰物引起。邻苯二甲酸酯是一类环境内分泌活性化学物质，已知通过减少胎鼠体内睾酮的产生来扰乱男性生殖道的发育。利用我们之前开发的器官培养系统，我们研究了邻苯二甲酸单-2-乙基己酯(MEHP)对人胎儿睾丸发育的影响。MEHP是一种工业化学品，存在于许多产品中，已被认为是男性生殖功能的干扰物。人胎儿睾丸在妊娠早期(7-12周)，睾丸分化的关键期，在基础条件下或在基础条件下加或不加MEHP或在黄体生成素(LH)刺激下培养3d。无论剂量是多少，MEHP治疗对体外培养的人胎儿睾丸产生的基础或促黄体生成素没有影响，尽管在我们的培养系统中可以调节睾酮的产生。MEHP(10−4 M)对支持细胞的增殖和凋亡无明显影响，但可降低抗苗勒氏激素的表达。MEHP(10−4 M)在不影响生殖细胞增殖的情况下，通过检测caspase3阳性生殖细胞来增加生殖细胞的凋亡，从而减少生殖细胞的数量。这是第一次实验证明邻苯二甲酸盐改变了人类生殖细胞谱系的发育。然而，与在大鼠身上观察到的结果相反，邻苯二甲酸盐并不影响类固醇的生成。
Several studies have described an increasing frequency of male reproductive disorders, which may have a common origin in fetal life and which are hypothesized to be caused by endocrine disruptors. Phthalate esters represent a class of environmental endocrine-active chemicals known to disrupt development of the male reproductive tract by decreasing testosterone production in the fetal rat. Using the organ culture system we developed previously, we investigated the effects on the development of human fetal testis of one phthalate—mono-2-ethylhexyl phthalate (MEHP)—an industrial chemical found in many products, which has been incriminated as a disruptor of male reproductive function. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation, a critical period for testicular differentiation, and cultured for 3 days with or without MEHP in basal conditions or stimulated with luteinizing hormone (LH). Whatever the dose, MEHP treatment had no effect on basal or LH-stimulated testosterone produced by the human fetal testis in vitro, although testosterone production can be modulated in our culture system. MEHP (10−4 M) did not affect proliferation or apoptosis of Sertoli cells, but it reduced the mRNA expression of anti-Müllerian hormone. MEHP (10−4 M) reduced the number of germ cells by increasing their apoptosis, measured by the detection of caspase-3–positive germ cells, without modification of their proliferation. This is the first experimental demonstration that phthalates alter the development of the germ cell lineage in humans. However, in contrast to results observed in the rat, phthalates did not affect steroidogenesis.
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影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
大鼠的胎儿睾丸外植体中邻苯二甲酸酯和邻苯二甲酸苯二甲酸苯甲酸苯甲酸苯甲酸苯胺苯酚的影响：与人体的新生大鼠和新生儿摩尔莫斯群的体内作用与人体的体内作用进行比较。
影响因子：
10.4
作者：
Hallmark, Nina;Walker, Marion;McKinnell, Chris;Mahood, I Kim;Scott, Hayley;Bayne, Rosemary;Coutts, Shiona;Anderson, Richard A;Greig, Irene;Morris, Keith;Sharpe, Richard M
通讯作者：
Sharpe, Richard M
影响因子：
3.8
作者：
Gunnarsson, David;Leffler, Per;Selstam, Gunnar
通讯作者：
Selstam, Gunnar
影响因子：
4.8
作者：
Delbès, R;Levacher, C;Habert, R
通讯作者：
Habert, R
影响因子：
4.8
作者：
Ferrara, Diana;Hallmark, Nina;Sharpe, Richard M.
通讯作者：
Sharpe, Richard M.