The potential for prenatal, early childhood and adolescent exposures to endocrine disrupting chemicals (EDCs) to adversely impact neural and reproductive development is a growing public health concern. Phthalates and BPA are EDCs that are used in many consumer products, and are regularly detected in human urine. Both chemicals are known to disrupt neural and reproductive development in animal models, but little is known about their potential to interfere with these developmental processes in humans. Additionally, a large percentage of reproductive age women and adolescent children in the US consume diets high in saturated fat (HFD) and are either overweight or obese. Recent evidence suggests that maternal obesity during the prenatal period or child obesity in the adolescent period may be linked to impaired neurological and reproductive function, but little is known about the potential for a HFD or obesity to interact with EDC exposure to increase risk. Project 1 has 4 aims that will address these critical public health questions: (1) it will assess sources of exposure to phthalates, BPA and other EDCs during the prenatal and adolescent periods;(2) it will use novel methods developed in our Formative Children's Center to assess the impact of exposure to EDCs during either the prenatal or adolescent period on child physical, behavioral and cognitive development;(3) it will assess the potential for HFD/obesity during either the prenatal or adolescent period to interact with chemical exposure to influence physical, behavioral and cognitive development;and (4) it will investigate the association between prenatal exposure to phthalates, BPA and other EDCs and markers of oxidative stress or inflammation in maternal and cord blood, as well as the potential for increases in oxidative stress and inflammation to mediate the impact of exposure on outcomes. A significant strength of conducting this research in the context of the proposed Center is that Projects 2 and 3 will conduct parallel rodent studies that will assess similar developmental endpoints in mice and rats exposed to phthalates or BPA either prenatally or during adolescence, allowing comparison of exposure-outcome relationships in animal and hurnan studies.

Public Health Relevance

Phthalates and bisphenol A are endocrine disrupting chemicals that are found in many consumer products. Exposure is widespread, but its impact on child health and development is not well-understood. This Project will fill an important gap in our knowledge by investigating the effects of these chemicals, both alone and combination with a high fat diet on physical and neurodevelopment.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Program Projects (P01)
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Special Emphasis Panel (ZES1-LWJ-K)
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University of Illinois Urbana-Champaign
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Zhou, Changqing; Gao, Liying; Flaws, Jodi A (2017) Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice. Toxicol Appl Pharmacol 318:49-57
Mahalingam, Sharada; Ther, Laura; Gao, Liying et al. (2017) The effects of in utero bisphenol A exposure on ovarian follicle numbers and steroidogenesis in the F1 and F2 generations of mice. Reprod Toxicol 74:150-157
Zhou, Changqing; Gao, Liying; Flaws, Jodi A (2017) Exposure to an Environmentally Relevant Phthalate Mixture Causes Transgenerational Effects on Female Reproduction in Mice. Endocrinology 158:1739-1754
Zhou, Changqing; Flaws, Jodi A (2017) Effects of an Environmentally Relevant Phthalate Mixture on Cultured Mouse Antral Follicles. Toxicol Sci 156:217-229
Barakat, Radwa; Lin, Po-Ching Patrick; Rattan, Saniya et al. (2017) Prenatal Exposure to DEHP Induces Premature Reproductive Senescence in Male Mice. Toxicol Sci 156:96-108
Berger, Amelia; Ziv-Gal, Ayelet; Cudiamat, Jonathan et al. (2016) The effects of in utero bisphenol A exposure on the ovaries in multiple generations of mice. Reprod Toxicol 60:39-52
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
Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching et al. (2016) Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System. Endocrinology 157:4579-4587
Li, Quanxi; Davila, Juanmahel; Kannan, Athilakshmi et al. (2016) Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy in Mice. Endocrinology 157:1764-74
Strakovsky, Rita S; Wang, Huan; Engeseth, Nicki J et al. (2015) Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis. Toxicol Appl Pharmacol 284:101-12

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