Early life, and especially prenatal, exposure to endocrine disrupting chemicals (EDCs) may be related to poor health outcomes later in life, including neurodevelopmental delays and disorders. Autism spectrum disorder (ASD) is a neurological disorder with high societal and personal impact, and of unknown but likely complex causes. Environmental factors are hypothesized to contribute to at least 50% of the risk of ASD but challenges in measuring human fetal exposure to EDCs, and in measuring endogenous metabolism relevant to the health effects of EDCs inhibits studying the relation of EDCs to ASD. Consequently, to enable effective investigation of the role of EDCs as ASD risk factors, comprehensive biomarker-based exposure assessment approaches need to be developed that 1) include highly sensitive measurement of internal dose and 2) incorporate measures of endogenous metabolism as well as early indicators of biologic response. This proposal will overcome these challenges in exposure science and develop the independent research career of a young investigator focused on environmental health sciences in these three specific aims;
Specific Aim 1. Quantify internal dose of prototypical EDC exposures (BPA, methylparaben, bis (2-ethylhexyl) phthalate, and vinclozolin) in controlled exposures in mice and human variable population exposures using developmentally relevant blood, urine, placenta, meconium and fetal tissue.
Specific Aim 2. Elucidate the influence of endogenous metabolic mediators of EDC exposure (sex hormones and folates) on a known biologically relevant exposure response (DNA methylation) during critical neurodevelopmental windows in EDC exposed mice and humans.
Specific Aim 3. Identify additional Candidate biomarkers of biological response to EDC exposure.
Prenatal exposure to endocrine disrupting chemicals (EDCs) may be related to poor health outcomes later in life, including neurodevelopmental delays and disorders. Challenges in measuring human fetal exposure to EDCs, and in measuring endogenous metabolism relevant to the health effects of EDCs inhibits studying the relation of EDCs to autism spectrum disorder (ASD). This proposal will overcome these challenges and develop the independent research career of a young investigator focused on environmental health sciences.
|Brodnik, Zachary D; Black, Emily M; Clark, Meagan J et al. (2017) Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine. Neuropharmacology 125:295-307|
|Pinney, Sara E; Mesaros, Clementina A; Snyder, Nathaniel W et al. (2017) Second trimester amniotic fluid bisphenol A concentration is associated with decreased birth weight in term infants. Reprod Toxicol 67:1-9|
|Frey, Alexander J; Park, Bo Y; Schriver, Emily R et al. (2017) Differences in testosterone and its precursors by sex of the offspring in meconium. J Steroid Biochem Mol Biol 167:78-85|
|Carrer, Alessandro; Parris, Joshua L D; Trefely, Sophie et al. (2017) Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation Levels. J Biol Chem 292:3312-3322|
|Liu, Jixia; Zhao, Ran; Ye, Zhan et al. (2017) Relationship of SULT1A1 copy number variation with estrogen metabolism and human health. J Steroid Biochem Mol Biol 174:169-175|
|Mesaros, Clementina; Arroyo, Alejandro D; Blair, Ian A et al. (2017) Coenzyme A thioester formation of 11- and 15-oxo-eicosatetraenoic acid. Prostaglandins Other Lipid Mediat 130:1-7|
|Xu, Rengyi; Mesaros, Clementina; Weng, Liwei et al. (2017) Comparison of statistical methods for detection of serum lipid biomarkers for mesothelioma and asbestos exposure. Biomark Med 11:547-556|
|Sims, Carrie; Salliant, Noelle; Worth, Andrew J et al. (2017) Metabolic tracing analysis reveals substrate-specific metabolic deficits in platelet storage lesion. Transfusion 57:2683-2689|
|Guo, Lili; Worth, Andrew J; Mesaros, Clementina et al. (2016) Diisopropylethylamine/hexafluoroisopropanol-mediated ion-pairing ultra-high-performance liquid chromatography/mass spectrometry for phosphate and carboxylate metabolite analysis: utility for studying cellular metabolism. Rapid Commun Mass Spectrom 30:1835-45|
|Frey, Alexander J; Feldman, Daniel R; Trefely, Sophie et al. (2016) LC-quadrupole/Orbitrap high-resolution mass spectrometry enables stable isotope-resolved simultaneous quantification and ¹³C-isotopic labeling of acyl-coenzyme A thioesters. Anal Bioanal Chem 408:3651-8|
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