Influence of endocrine active compounds on the developing rodent brain

Department of Zoology, North Carolina State University, 127 David Clark Labs, Raleigh, NC 27695, USA.
Brain Research Reviews (Impact Factor: 5.93). 04/2008; 57(2):352-62. DOI: 10.1016/j.brainresrev.2007.06.008
Source: PubMed


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.

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Available from: Heather B Patisaul, Jul 28, 2014
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    • "We also focused here on males. Fetal exposure of females to BPA leads to a different set of outcomes due to the effects of endogenous estradiol after puberty and the fact that developmental exposure to BPA alters the functioning of the female neuroendocrine system [23] [44]; data from female siblings will be reported elsewhere. "
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    • "Moreover, depending on the developmental timing of specific brain structures and their coincident exposure to the prevailing steroidal milieu, some brain structures may be demasculinized/defeminized, whereas others are not. In addition, the causes of variations could relate to individual genetic variability or exposure to environmental factors that suppress the reproductive axis (e.g., stress) or disrupt hormone actions (e.g., environmental endocrine disruptors; Ryan and Vandenbergh, 2002; Patisaul and Polston, 2008). This manuscript will review major findings that support the hypothesis that the organizational actions of sex steroids are responsible for sexual differentiation of sexual partner preferences in select non-human species and explore how this work has informed and helped to frame our understanding of biological influences on human sexual orientation and gender identity. "
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