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.

Download full-text


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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Of the approximately 85,000 chemicals in use, 1000 have been identified as having the ability to disrupt normal endocrine function. Exposure to endocrine disrupting chemicals (EDCs) during critical period in brain differentiation (prenatal and neonatal life) via the mother can alter the course of the development of sexually dimorphic behaviors. Bisphenol A (BPA) is a very high volume chemical used in plastic, resins and other products, and virtually everyone examined has detectable BPA. BPA has estrogenic activity and is one of the most studied EDCs. We review evidence from studies in rodents using dose levels relevant to human exposure. BPA alters behavior and eliminates or in some cases reverses sexually dimorphic behaviors observed in unexposed animals.
    No preview · Article · Dec 2015
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Phenols are uremic toxins of intestinal origin formed by bacteria during protein metabolism. Of these molecules, p-cresol is the most studied and has been associated with renal function impairment and vascular damage. Bisphenol A (BPA) is a molecule with structural similarity with phenols found in plastic food and beverage containers as well as in some dialyzers. BPA is considered an environmental toxicant based on animal and cell culture studies. Japanese authorities recently banned BPA use in baby bottles based on observational association studies in newborns. BPA is excreted in urine and uremic patients present higher serum levels, but there is insufficient evidence to set cut-off levels or to link BPA to any harmful effect in CKD. However, the renal elimination and potential exposure during dialysis warrant the monitoring of BPA exposure and the design of observational studies in which the potential health risks of BPA for end-stage renal disease patients are evaluated.
    Full-text · Article · Jul 2013 · International Journal of Nephrology
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 - 50,000μg/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2-200pg/ml in fetal serum (AUC0-24h), we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose-response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-μg/kg/day dose of DES resulted in some but not all low-dose BPA outcomes.
    Full-text · Article · Jul 2013 · Reproductive Toxicology
Show more