There continues to be an increase in the incidence and prevalence of neurobehavioral disorders. Considerable evidence has accumulated linking environmental toxicants, including pesticides, to these disorders and generally to detriments in neurobehavioral development. The placenta serves as a conduit of maternal signals and directs the developmental program through key roles it plays in nutrient transfer, metabolism, gas exchange, neuroendocrine signaling, growth hormone production, and immunologic control. These critical functions may be controlled by, as well as be reflected in, placenta genomics. Data from our group and others have demonstrated that environmental exposures including chemical and psychosocial factors can impact these placental functions reflected in variation in the molecular character of the placenta. Pyrethroid pesticides are a group of common insecticides and due to their persistence and widespread use are found with high prevalence throughout human populations. Increased pyrethroid exposures have been linked to a greater risk for attention deficit hyperactivity disorder (ADHD) in children as well as to cognitive defects. These insecticides can accumulate in and transfer through mammalian placentas and prenatal exposures have been linked to altered placental and neuronal functions including effects on the dopaminergic system. The scientific premise of this project is that the prenatal environment can disrupt critical functions of the placenta, reflected in placental gene networks, leading to alterations in communication of environmental signals between mother and fetus, and ultimately the development of postnatal health and disease. Thus, the placenta is the central organ for the developmental origins of health and diseases (DOHaD) paradigm. We specifically hypothesize that disruption of gene networks in the placenta by in utero exposures to common pyrethroids acts as a mediator of the impact leading to cognition and behavior deficit in the offspring. In a prospective pregnancy and birth cohort, with a primary focus on effects of prenatal pesticide exposure on newborn and early life neurobehavioral function, we will thoroughly interrogate the placenta genome to provide evidence for the molecular underpinnings of these effects. In parallel, we will utilize a highly characterized murine model of exposure to the one common pyrethroid, i.e. deltamethrin, to provide causal evidence of these placental genomic features as mediators of the environment?s effect on offspring neurodevelopment, and more importantly, to shed lights on relevance of placental gene networks to the programming in the brain, which will also be comprehensively interrogated. Our innovative, integrated modelling takes advantage of this bidirectional translational research approach and will provide an opportunity to define prevention or intervention strategies that can optimize the chances for successful pregnancy and health outcomes in children, as well as define novel biomarkers to classify risk at the earliest points in life so that interventions can be employed when they are most effective.

Public Health Relevance

The placenta serves as the regulator of fetal development and this project will examine how exposures to common pesticides can alter the placenta?s function to impact offspring neurological and behavioral outcomes. Such findings may have significant clinical and public health impact, providing an opportunity for early interventions for at-risk children, and potentially identifying novel paths for prevention and treatment of common neurobehavioral disorders.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZES1)
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Schug, Thaddeus
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Emory University
Public Health & Prev Medicine
Schools of Public Health
United States
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Everson, Todd M; Marsit, Carmen J (2018) Integrating -Omics Approaches into Human Population-Based Studies of Prenatal and Early-Life Exposures. Curr Environ Health Rep 5:328-337
Lester, Barry M; Marsit, Carmen J (2018) Epigenetic mechanisms in the placenta related to infant neurodevelopment. Epigenomics 10:321-333