Institut national de la santé et de la recherche médicale, IRSET, U1085, Campus de Beaulieu, F-35042 Rennes CEDEX, France.
Hum Reprod. 2012 May;27(5):1451-9. doi: 10.1093/humrep/des069. Epub 2012 Mar 8.
Phthalic acid esters are widely used in the manufacture of plastics. Numerous studies have shown that these phthalates impair testicular testosterone production in the rat. However, the scarce and contradictory data concerning humans have cast doubt over whether these compounds are also anti-androgenic in man. We therefore investigated the direct effects of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) on organo-cultured adult human testis and a human cell line.
Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with DEHP or MEHP. The effects of ketoconazole, used as a reference molecule, were also assessed.
In both models, DEHP and MEHP significantly inhibited testosterone production. The effects of both phthalates appeared to be specific for steroidogenesis, as INSL3 production by Leydig cells was not altered. Furthermore, the phthalates of interest had no effect on inhibin B production by Sertoli cells or on germ cell apoptosis. As only a small fraction of the phthalates added was found in the testis explants, and as these compounds were found to be metabolized, we estimate that the anti-androgenic effects observed occurred at concentrations of phthalates that are of the same order of magnitude as exposures reported in the literature for men.
We provide the first evidence that DEHP and MEHP can inhibit testosterone production in the adult human testis. This is consistent with recent epidemiological findings of an inverse correlation between exposure to MEHP and testosterone concentrations.
邻苯二甲酸酯广泛应用于塑料制造。大量研究表明，这些邻苯二甲酸酯会损害大鼠睾丸中的睾酮产生。然而，关于人类的稀缺且相互矛盾的数据，使人怀疑这些化合物是否也具有抗雄激素作用。因此，我们研究了邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸单（2-乙基己基）酯（MEHP）对成人人类睾丸器官培养物和人类细胞系的直接影响。
将 DEHP 或 MEHP 与成人睾丸组织外植体或 NCI-H295R 肾上腺皮质人细胞一起培养。还评估了酮康唑的作用，酮康唑被用作参考分子。
在这两种模型中，DEHP 和 MEHP 均显著抑制了睾酮的产生。这两种邻苯二甲酸酯的作用似乎对类固醇生成具有特异性，因为 Leydig 细胞的 INSL3 产生没有改变。此外，感兴趣的邻苯二甲酸酯对支持细胞的抑制素 B 产生或生殖细胞凋亡没有影响。由于仅在睾丸外植体中发现添加的邻苯二甲酸酯的一小部分，并且这些化合物被发现被代谢，我们估计观察到的抗雄激素作用发生在与文献中报道的男性暴露量相同数量级的邻苯二甲酸酯浓度下。
我们提供了第一个证据，证明 DEHP 和 MEHP 可以抑制成人人类睾丸中的睾酮产生。这与最近关于 MEHP 暴露与睾酮浓度之间存在反比关系的流行病学发现一致。
