Common chemicals in the environment have the potential to disrupt the role of gonadal hormones during human development. Examples include the widely used chemicals bisphenol A, which is estrogenic, and the phthalates, which are anti-androgenic. Both chemicals are the focus of this formative center proposal. Besides the potential consequences for reproductive functions, cognitive neural functions, which are also influenced by gonadal hormones, may be altered by these endocrine disruptors. The present pilot project is preliminary and within its limited scope and budget, will initially model the effects of only bisphenol A in hooded rats, an animal model where sex differences in the cerebral cortex have been documented and are known to be influenced by hormonal milieu during both the perinatal and peripubertal period. The effects of bisphenol A on neuron number, a very basic building block of function, will be explored in two cortical areas of rats, the visual cortex and the medial prefrontal cortex (PL and IL) where sex differences have been found . Separate groups of animals will be exposed to 0, 4, 40 or 400 """"""""mu""""""""g/kg/day perinatally or peripubertally. When the rats reach adulthood, the number of neurons in each cortical area will be quantified with stereological methods. In addition to their established sex differences in neuron number, these cortical regions play a role in behaviors analogous to those that will be assessed in human infants and adolescents in Projects 1 and 2. The behavioral consequences of cortical alterations will also be investigated in a visual spatial task, the radial arm maze, which consistently shows sex differences in several laboratories. As adults, all rats will be tested on a 17-arm radial maze with both baited and unbaited arms so that both reference and working memory can be tested. Within animal comparisons between behavioral performance and neuron number will be made.

Public Health Relevance

This preliminary project is a start at investigating whether the effects of common endocrine disruptors, here bisphenol A, go beyond reproduction function to higher order cognitive functions. Disruption of cortical development could have implciations for normative cogntive development as well as a host of syndromes with a cortical/cognitive component such as schizophrenia and autism.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Exploratory Grants (P20)
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Special Emphasis Panel (ZES1-LKB-G)
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University of Illinois Urbana-Champaign
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Wise, Leslie M; Sadowski, Renee N; Kim, Taehyeon et al. (2016) Long-term effects of adolescent exposure to bisphenol A on neuron and glia number in the rat prefrontal cortex: Differences between the sexes and cell type. Neurotoxicology 53:186-192
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Sadowski, R N; Wise, L M; Park, P Y et al. (2014) Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females. Neuroscience 279:122-31
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Sadowski, Renee N; Park, Pul; Neese, Steven L et al. (2014) Effects of perinatal bisphenol A exposure during early development on radial arm maze behavior in adult male and female rats. Neurotoxicol Teratol 42:17-24
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Peretz, Jackye; Flaws, Jodi A (2013) Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles. Toxicol Appl Pharmacol 271:249-56
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Peretz, Jackye; Craig, Zelieann R; Flaws, Jodi A (2012) Bisphenol A inhibits follicle growth and induces atresia in cultured mouse antral follicles independently of the genomic estrogenic pathway. Biol Reprod 87:63
Brannick, Katherine E; Craig, Zelieann R; Himes, Ashley D et al. (2012) Prenatal exposure to low doses of bisphenol A increases pituitary proliferation and gonadotroph number in female mice offspring at birth. Biol Reprod 87:82

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