Endocrine disruptors are chemicals that can interfere with hormonal functions and many are found in widely used consumer products. Hormones play a critical role in the formation ofthe nervous system, which makes it vulnerable to these common chemicals. Two ofthe major examples of endocrine disruptors, the phthalates and bisphenol A (BPA), are known to disrupt both the gonadal steroids and thyroid function. Both chemicals are the focus of this proposal using a rodent model. Increases in body weight are found with exposures to the phthalates and BPA, and this weight gain is exacerbated by high fat diets. High fat diets alone interfere with cognition in both rodents and human children. BPA and the phthalates, as well as high fat diets, all increase oxidative stress and inflammation, and these environmental factors can have epigenetic effects. We hypothesize that the combination of the exposure to endocrine disruptors and a high fat diet during development will be especially pernicious for cognitive behavior and the neural regions of the brain that are important for this behavior, such as the cerebral cortex. The experimental design entails exposure to either a phthalate mixture or BPA with or without a concurrent high fat diet. Two different times during development are targeted in the two Aims.
Aim 1 examines the long-term effects after exposure during pre- and post-natal development when the nervous system is rapidly changing.
Aim 2 examines exposure during adolescence, a time when the final growth and pruning ofthe nervous system occurs, especially in the prefrontal area of the cerebral cortex. The end point for both of these aims will be the number of neurons, the number and types of glia including microglia (which increase with inflammation) and dopaminergic innervation through immunolabeling of tyrosine hydroxylase in the medial prefrontal cortex. Tests of cognition will include object recognition and intra- and extra-dimensional shifts. There will be accompanying measurements of body weight and fat composition and indices of oxidative stress, inflammation and epigenetic changes in these markers.
Endocrine disruptors are ubiquitous in the environment as are high fat diets, and both of these environmental factors could disturb the normal development ofthe nervous system, during early development and during adolescence. This will be directly examined in a rodent model so that the cellular and molecular mechanisms ofthe effects can be elucidated.
|Ziv-Gal, Ayelet; Flaws, Jodi A (2016) Evidence for bisphenol A-induced female infertility: a review (2007-2016). Fertil Steril 106:827-56|
|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 53:186-92|
|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|
|Ziv-Gal, Ayelet; Wang, Wei; Zhou, Changqing et al. (2015) The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice. Toxicol Appl Pharmacol 284:354-62|
|Strakovsky, Rita S; Lezmi, StÃ©phane; Shkoda, Ielyzaveta et al. (2015) In utero growth restriction and catch-up adipogenesis after developmental di (2-ethylhexyl) phthalate exposure cause glucose intolerance in adult male rats following a high-fat dietary challenge. J Nutr Biochem 26:1208-20|
|Dzwilewski, Kelsey L C; Schantz, Susan L (2015) Prenatal chemical exposures and child language development. J Commun Disord 57:41-65|
|Zhou, Changqing; Wang, Wei; Peretz, Jackye et al. (2015) Bisphenol A exposure inhibits germ cell nest breakdown by reducing apoptosis in cultured neonatal mouse ovaries. Reprod Toxicol 57:87-99|
|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|
|Niermann, Sarah; Rattan, Saniya; Brehm, Emily et al. (2015) Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice. Reprod Toxicol 53:23-32|
Showing the most recent 10 out of 13 publications