Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny
Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny
复制标题
DOI：
10.1098/rspb.2013.1532
复制
发表时间：
2013-10-07
影响因子：
4.7
通讯作者：
Eustache, Florence
中科院分区：
文献类型：
--
作者：
Auger, Jacques;Le Denmat, Dominique;Eustache, Florence
在包括人类在内的许多物种中，指长比，特别是第二到第四指比(2D：4D)，与各种病理和行为状况有关，并依赖于产前雄激素与雌激素的平衡。目前尚不清楚数字比率是否会因环境暴露于无处不在的内分泌干扰物而改变。我们研究了低剂量雌激素和抗雄激素化合物双酚A(BPA)、金雀异黄素和长春花碱对成年雄性Wistar大鼠手指比率的影响，并同时调查了这一特征的可能的性二型性。我们还调查了孕期不暴露对雄性后代的影响。拍摄左、右前爪X线片，采用基于半自动图像分析的标准化方法测量2D-5D近节距远端指骨距离。我们提供的证据表明，Wistar大鼠的手指比例存在性别二型性，我们发现BPA单独或与染料木素和长春花碱联合使用显著地使雄性大鼠的手指比例女性化。有趣的是，在接触了化合物混合物的雄性未暴露的雄性后代中，也发现了手指比例的显著女性化。总而言之，出生前环境中内分泌活性物质的水平永久性地破坏了数字比率。因此，成人的数字比率测量是一种有希望的啮齿动物出生前暴露于低剂量内分泌干扰物的生物标志物，对未来的人类研究具有潜在的意义。
Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D-5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans.