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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Career Transition Award (K22)
Project #
5K22ES026235-03
Application #
9447167
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Lawler, Cindy P
Project Start
2016-02-01
Project End
2019-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Drexel University
Department
Type
Organized Research Units
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19102
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