Article

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

ABSTRACT

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
    • "The cerebral cortex, hippocampus and hypothalamus are key sexually dimorphic regions in the rodent brain, and these brain areas are affected by prenatal and perinatal EDCs exposure, with sex specific effects observable even before the increase in gonadal hormones during puberty. Here we will refer only to a few relevant examples of the impact of BPA exposure on brain sexual differentiation.The developing hypothalamus has sex specific vulnerability to BPA, with the preoptic area (POA) and mediobasal hypothalamus (MBH) being the most studied and robustly affected4445464748. The hypothalamic monoaminergic systems as well as the neurohypophiseal neuropeptides (oxytocin and vasopressin) seem to be additional functional targets of developmental exposure to EDCs[10,17]. "
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    • "Exposure in utero or perinatally to BPA can lead to permanent behavioral disorders in rodents, including increased levels of aggression and anxiety and alterations in learning, memory, exploration, and emotional responsiveness [55]. Several mouse studies concluded that maternal exposure to low-dose BPA has long-term consequences on neurobehavioral development [56] and neonatal exposure to BPA can affect brain morphology and neuronal adult phenotypes [57]. "
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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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