Service d'Histologie-Embryologie, Biologie de Reproduction and Centre d'Etude et de Conservation des Œufs et du Sperme Humain, Site Port-Royal, Hôpitaux Universitaires Paris Centre, 75014 Paris, France.
Proc Biol Sci. 2013 Aug 7;280(1768):20131532. doi: 10.1098/rspb.2013.1532. Print 2013 Oct 7.
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.
指长比，尤其是第二到第四指长比（2D：4D），与许多物种（包括人类）的各种病理和行为状况有关，并且依赖于产前雄激素与雌激素的平衡。目前尚不清楚环境中暴露于普遍存在的内分泌干扰物是否会改变指长比。我们研究了低剂量的雌激素和抗雄激素化合物双酚 A（BPA）、金雀异黄素和萎地唑啉在妊娠期暴露对雄性 Wistar 大鼠指长比的影响，并在平行研究中研究了这种特征的可能性别二态性。我们还研究了未在妊娠期暴露的雄性后代的影响。我们对左、右前爪进行 X 射线拍摄，并通过基于半自动图像分析的标准化程序测量近节指骨到远节指骨的 2D-5D 近端到远端距离。我们提供的证据表明，Wistar 大鼠存在指长比的性别二态性，我们发现 BPA 单独或与金雀异黄素和萎地唑啉联合使用显著使雄性大鼠的指长比女性化。有趣的是，在雄性大鼠暴露于混合化合物的未暴露雄性后代中，也发现了指长比的显著女性化。总之，产前环境水平的内分泌活性物质会永久性地破坏指长比。因此，在成年动物中测量指长比是一种有前途的生物标志物，可以用于检测啮齿动物低剂量内分泌干扰物的产前暴露，这可能对未来的人类研究产生影响。
