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Review of recent experimental evidence: phthalates and male reproductive endpoaints

机译：近期实验证据回顾：邻苯二甲酸盐和男性生殖内分泌

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The antiandrogenic properties of phthalates and their characterization as testicular developmental toxicants have been derived from a series of experimental studies in the rat. Effects of developmental exposure in the rat include decreased anogenital distance, hypospermatogenesis, underdeveloped reproductive organs, cryptorchidism and hypospadias, and formation of multinucleated germ cells (MNG) in the testis. The underlying mechanism is related to the suppression of testosterone production in Leydig cells in the rat testis. The mouse, however, did not show suppression of steriodogenesis and reproductive organ malformations, but did show MNG formation. Also in marmosets, phthalates did not affect reproductive organ development, nor did testicular histopathology reveal abnormalities. The human testicular developmental response to phthalates has been difficult to address experimentally for ethical reasons and due to the absence of appropriate alternative models. Two independent recent studies have used xenotransplants of human fetal testis in immunologically compromised rodents to study the effects of phthalate exposure in man. Both studies found no effects on steroidogenesis whereas MNG were induced in both models in human fetal testis implants, confirming adequate internal exposure of implanted target tissue. Moreover, in the same model, steroidogenesis in mouse implants was unaffected as well, although MNG were observed. Rat implants showed suppression of steroidogenesis as well as MNG formation, confirming the general sensitivity of the model as in the in vivo situation. These results strongly suggest that human fetal testicular tissue is not sensitive to the endocrine disrupting effects of phthalates.
机译：邻苯二甲酸酯的抗雄激素特性及其作为睾丸发育毒性剂的特性已从大鼠的一系列实验研究中衍生而来。大鼠发育性暴露的影响包括肛门生殖器距离缩短，精子发生不足，生殖器官发育不足，隐睾症和尿道下裂以及睾丸中多核生殖细胞（MNG）的形成。潜在的机制与抑制大鼠睾丸Leydig细胞中睾丸激素的产生有关。然而，小鼠并未显示出抑制成骨细胞和生殖器官畸形的作用，但确实显示出了MNG的形成。同样在mar猴中，邻苯二甲酸盐也不会影响生殖器官的发育，睾丸的组织病理学也不会显示异常。由于伦理学原因并且由于缺乏合适的替代模型，人类对邻苯二甲酸酯的睾丸发育反应很难通过实验解决。最近两项独立的研究在免疫受损的啮齿动物中使用了人类胎儿睾丸的异种移植，以研究邻苯二甲酸酯对人体的影响。两项研究均未发现对类固醇生成有影响，而两种模型均在人类胎儿睾丸植入物中诱导了MNG，这证实了植入的目标组织有足够的内部暴露。此外，在同一模型中，尽管观察到了MNG，但小鼠植入物中的类固醇生成也未受影响。大鼠植入物显示出类固醇生成以及MNG形成的抑制，证实了该模型在体内情况下的总体敏感性。这些结果强烈表明人胎儿睾丸组织对邻苯二甲酸酯的内分泌干扰作用不敏感。

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