Patisaul Heather B, Polston Eva K
Department of Zoology, North Carolina State University, 127 David Clark Labs, Raleigh, NC 27695, USA.
Brain Res Rev. 2008 Mar;57(2):352-62. doi: 10.1016/j.brainresrev.2007.06.008. Epub 2007 Aug 3.
Changes in the volumes of sexually dimorphic brain nuclei are often used as a biomarker for developmental disruption by endocrine-active compounds (EACs). However, these gross, morphological analyses do not reliably predict disruption of cell phenotype or neuronal function. Therefore, an experimental approach that simultaneously assesses anatomical, physiological and behavioral endpoints is required when developing risk assessment models for EAC exposure. Using this more comprehensive approach we have demonstrated that the disruption of nuclear volume does not necessarily coincide with disruption of cellular phenotype or neuroendocrine function in two sexually dimorphic brain nuclei: the anteroventral periventricular nucleus of the hypothalamus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN). These results demonstrate that nuclear volume is likely not an appropriate biomarker for EAC exposure. We further demonstrated that neonatal exposure to the EACs genistein (GEN) and Bisphenol-A (BPA) can affect sexually dimorphic brain morphology and neuronal phenotypes in adulthood with regional and cellular specificity suggesting that effects observed in one brain region may not be predictive of effects within neighboring regions. Finally, developmental EAC exposure has been shown to affect a variety of sexually dimorphic behaviors including reproductive behavior. These effects are likely to have a broad impact as maladaptive behavior could translate to decreased fitness of entire populations. Collectively, these findings emphasize the need to employ a comprehensive approach that addresses anatomical, functional and behavioral endpoints when evaluating the potential effects of EAC exposure.
性二态性脑核体积的变化常被用作内分泌活性化合物（EACs）对发育造成干扰的生物标志物。然而，这些粗略的形态学分析并不能可靠地预测细胞表型或神经元功能的破坏。因此，在开发EAC暴露风险评估模型时，需要一种能同时评估解剖学、生理学和行为学终点的实验方法。通过使用这种更全面的方法，我们证明了在两个性二态性脑核：下丘脑室旁前腹侧核（AVPV）和视前区性二态核（SDN）中，核体积的破坏不一定与细胞表型或神经内分泌功能的破坏同时发生。这些结果表明，核体积可能不是EAC暴露的合适生物标志物。我们进一步证明，新生期暴露于EACs染料木黄酮（GEN）和双酚A（BPA）可在成年期影响性二态性脑形态和神经元表型，具有区域和细胞特异性，这表明在一个脑区观察到的效应可能无法预测相邻区域内的效应。最后，发育过程中EAC暴露已被证明会影响多种性二态性行为，包括生殖行为。这些影响可能具有广泛的影响，因为适应不良行为可能会导致整个种群的适应性下降。总的来说，这些发现强调了在评估EAC暴露的潜在影响时，需要采用一种综合方法来解决解剖学、功能和行为学终点问题。
