ABSTRACT
Polycyclic aromatic hydrocarbons are a class of compounds found ubiquitously in air pollution secondary
to incomplete combustion of organic material. Sources of PAH include motor traffic, heating, tobacco
smoke, and grilled or charred food. Prenatal exposure to (PAH) is known to increase the risk of
neurodevelopmental disorders. Research to investigate the mechanisms of PAH-related neurotoxicity has
implicated mitochondrial function without resolving the details that would enable the development of
preventive or therapeutic interventions. To fill this critical gap, we propose an integrated set of
epidemiological and experimental aims to clarify the role of PAH-related mitochondrial DNA (mtDNA)
toxicity in early development. Previous study of prenatal PAH exposure and mitochondria has relied on
the use of mitochondrial DNA copy number (mtDNAcn) with mixed findings and limited interpretability.
We intend to supplement analysis of mtDNAcn with quantification of superoxide production and
mitochondrial membrane potential to understand the functional implications of the mtDNAcn biomarker
in this research. In the epidemiological approach, I will investigate the effects of prenatal PAH exposure
on mitochondrial indicators in umbilical cord blood and tissue samples from two prospective urban New
York City-based birth cohorts. In the parallel toxicological approach, I will use an experimental system of
mouse preimplantation embryos exposed to a PAH mixture that approximates the composition of cohort
exposure. This experimental system permits the observation mitochondrial effects of prenatal PAH
exposure during the critical window of very early development which are essentially impossible to
measure in humans. My project integrates two complementary approaches to address issues of
confounding, temporality, and species relevance found in single method studies and has the potential to
inform future research aimed at developing treatments or prevention strategies that have the potential to
reduce PAH-related neurotoxicity.
Polycyclic aromatic hydrocarbons are a class of compounds found ubiquitously in air pollution secondary
to incomplete combustion of organic material. Sources of PAH include motor traffic, heating, tobacco
smoke, and grilled or charred food. Prenatal exposure to (PAH) is known to increase the risk of
neurodevelopmental disorders. Research to investigate the mechanisms of PAH-related neurotoxicity has
implicated mitochondrial function without resolving the details that would enable the development of
preventive or therapeutic interventions. To fill this critical gap, we propose an integrated set of
epidemiological and experimental aims to clarify the role of PAH-related mitochondrial DNA (mtDNA)
toxicity in early development. Previous study of prenatal PAH exposure and mitochondria has relied on
the use of mitochondrial DNA copy number (mtDNAcn) with mixed findings and limited interpretability.
We intend to supplement analysis of mtDNAcn with quantification of superoxide production and
mitochondrial membrane potential to understand the functional implications of the mtDNAcn biomarker
in this research. In the epidemiological approach, I will investigate the effects of prenatal PAH exposure
on mitochondrial indicators in umbilical cord blood and tissue samples from two prospective urban New
York City-based birth cohorts. In the parallel toxicological approach, I will use an experimental system of
mouse preimplantation embryos exposed to a PAH mixture that approximates the composition of cohort
exposure. This experimental system permits the observation mitochondrial effects of prenatal PAH
exposure during the critical window of very early development which are essentially impossible to
measure in humans. My project integrates two complementary approaches to address issues of
confounding, temporality, and species relevance found in single method studies and has the potential to
inform future research aimed at developing treatments or prevention strategies that have the potential to
reduce PAH-related neurotoxicity.