Eladak Soria, Grisin Tiphany, Moison Delphine, Guerquin Marie-Justine, N'Tumba-Byn Thierry, Pozzi-Gaudin Stéphanie, Benachi Alexandra, Livera Gabriel, Rouiller-Fabre Virginie, Habert René
Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France.
Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital A. Béclère, Université Paris Sud, Clamart, France.
Fertil Steril. 2015 Jan;103(1):11-21. doi: 10.1016/j.fertnstert.2014.11.005. Epub 2014 Dec 2.
Bisphenol A (BPA) is a widely studied typical endocrine-disrupting chemical, and one of the major new issues is the safe replacement of this commonly used compound. Bisphenol S (BPS) and bisphenol F (BPF) are already or are planned to be used as BPA alternatives. With the use of a culture system that we developed (fetal testis assay [FeTA]), we previously showed that 10 nmol/L BPA reduces basal testosterone secretion of human fetal testis explants and that the susceptibility to BPA is at least 100-fold lower in rat and mouse fetal testes. Here, we show that addition of LH in the FeTA system considerably enhances BPA minimum effective concentration in mouse and human but not in rat fetal testes. Then, using the FeTA system without LH (the experimental conditions in which mouse and human fetal testes are most sensitive to BPA), we found that, as for BPA, 10 nmol/L BPS or BPF is sufficient to decrease basal testosterone secretion by human fetal testes with often nonmonotonic dose-response curves. In fetal mouse testes, the dose-response curves were mostly monotonic and the minimum effective concentrations were 1,000 nmol/L for BPA and BPF and 100 nmol/L for BPS. Finally, 10,000 nmol/L BPA, BPS, or BPF reduced Insl3 expression in cultured mouse fetal testes. This is the first report describing BPS and BPF adverse effects on a physiologic function in humans and rodents.
双酚A（BPA）是一种经过广泛研究的典型内分泌干扰化学物质，其中一个主要的新问题是安全替代这种常用化合物。双酚S（BPS）和双酚F（BPF）已经或计划用作双酚A的替代品。利用我们开发的培养系统（胎儿睾丸试验[FeTA]），我们先前表明，10 nmol/L的双酚A会降低人胎儿睾丸外植体的基础睾酮分泌，并且大鼠和小鼠胎儿睾丸对双酚A的敏感性至少低100倍。在这里，我们表明在FeTA系统中添加促黄体生成素（LH）可显著提高小鼠和人类胎儿睾丸中双酚A的最低有效浓度，但对大鼠胎儿睾丸则不然。然后，使用不含LH的FeTA系统（小鼠和人类胎儿睾丸对双酚A最敏感的实验条件），我们发现，与双酚A一样，10 nmol/L的BPS或BPF足以降低人胎儿睾丸的基础睾酮分泌，且剂量反应曲线通常是非单调的。在胎儿小鼠睾丸中，剂量反应曲线大多是单调的，双酚A和BPF的最低有效浓度为1000 nmol/L，BPS为100 nmol/L。最后，10000 nmol/L的双酚A、BPS或BPF降低了培养的小鼠胎儿睾丸中胰岛素样肽3（Insl3）的表达。这是第一份描述BPS和BPF对人类和啮齿动物生理功能产生不良影响的报告。
