This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A.
SPECIFIC AIMS The developmental origins of disease hypothesis is supported by numerous epidemiological and animal studies which suggest that adverse prenatal factors are associated with increased risk in adult life for obesity, hypertension, Type II diabetes, and metabolic syndrome (1-4). Although these cardiovascular, endocrine and metabolic outcomes are the most commonly investigated with respect to early origins of disease, asthma and other respiratory disorders are also affected by early exposures (5, 6). These prenatal influences likely exert their phenotypic effects through epigenetic changes (i.e. altered genetic expression) rather than through alteration of the primary DNA sequence (7, 8). Epigenetic factors may play an important role in mediating the environmental, genetic, and gene-environment risk factors for chronic diseases. Modifications such as DNA hypo- or hyper-methylation have been shown to occur in response to maternal exposures, and such changes are relevant to risk for chronic disease (5, 9). Although epigenetic changes can occur throughout life, they occur predominantly during gestation and shortly after birth (8). Exposure to biologics, particularly mold, dust mites, and cockroach, rodent and pet allergens, have been putatively associated with the induction of asthma in childhood (10-12). Strong evidence exists for the role of environmental tobacco smoke (ETS) in the induction of asthma (13). Importantly, cohort studies have demonstrated that in utero exposures (i.e., maternal smoking during pregnancy) are associated with subsequent asthma risk in the child (14-17). The role of ambient particulate matter (PM) or other ambient pollutants in asthma induction is less clear (13). Indoor-generated biomass smoke is an ideal particulate source for the investigation of PM-induced epigenetic changes and consequent effects on risk for chronic disease. Woodstoves are a common source of heating in many rural communities, and we have shown that such homes have moderately elevated indoor PM concentrations (18). Maternal environmental exposures to inhaled particulates should not be considered in isolation, however. Maternal diet may play a role in epigenetic modifications of the developing fetus and may also be relevant to childhood risk for asthma. Several lines of evidence, including our own research in Native American communities, support an association between obesity and asthma, but the causal and mechanistic nature of this relationship is not well understood (2, 19-21). Importantly, high birth weight has been associated with both asthma and adult obesity(22). Thus, prenatal nutrition could be an important factor in subsequent development of asthma and obesity. The mechanisms by which these relationships occur are unclear, but epigenetic events in response to the gestational environment are suspected to play a role (23, 24). The central hypothesis is that in utero exposure to biomass smoke and maternal dietary factors result in epigenetic changes that are associated with increased risk for development of childhood asthma. This pilot project represents a departure from our currently funded line of research but also represents a logical transition to understanding the early life risk factors associated with the development of asthma. This project will result in the generation of preliminary data, proof of principal, and demonstration of capacity to work with and collect biological samples from pregnant women and neonatal populations. Ultimately, our goal is to continue this research by submitting an R21 or R01 to NIEHS.
Specific Aim 1. Maternal and newborn blood samples will be evaluated via genome-wide methylation analysis to identify commonly methylated targets from smoke exposure and/or diet. The following descriptive analyses will be conducted: (1a) Targets of hyper- and hypo-methylation will be identified in blood samples with respect to gestational biomass smoke exposure and (1b) Targets of hyper- and hypo-methylation will be identified in blood samples with respect to maternal methyl supplementation and/or high fat maternal diet.
Specific Aim 2. Infants will be prospectively followed for six months to assess early life respiratory symptoms and respiratory infections. The following hypotheses will be assessed: (2a) Frequency of infant symptoms (e.g., cough, wheeze) and infections (e.g., RSV) will be associated with gestational biomass smoke exposure;and (2b) Frequency of infant symptoms (e.g., cough, wheeze) and infections (e.g., RSV) will be associated with maternal methyl supplementation and/or high fat maternal diet. Exploratory Aim (EA). Demonstration of capacity to collect additional biological samples from these populations will provide strong support for a future grant application. The following objectives will be assessed. EA1. Placental tissue and cord blood samples will be collected for future methylation analysis. EA2. Buccal cells will be collected from maternal/infant pairs for future DNA isolation and analysis.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-5 (01))
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University of Montana
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Schools of Pharmacy
United States
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Biswas, Rupa; Trout, Kevin L; Jessop, Forrest et al. (2017) Imipramine blocks acute silicosis in a mouse model. Part Fibre Toxicol 14:36
Sanchez-Contreras, Monica; Cardozo-Pelaez, Fernando (2017) Age-related length variability of polymorphic CAG repeats. DNA Repair (Amst) 49:26-32
Park, Sunyoung; Nevin, Andrew B C; Cardozo-Pelaez, Fernando et al. (2016) Pb exposure prolongs the time period for postnatal transient uptake of 5-HT by murine LSO neurons. Neurotoxicology 57:258-269
Jessop, Forrest; Hamilton, Raymond F; Rhoderick, Joseph F et al. (2016) Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure. Toxicol Appl Pharmacol 309:101-10
Gábriel, Robert; Erdélyi, Ferenc; Szabó, Gábor et al. (2016) Ectopic transgene expression in the retina of four transgenic mouse lines. Brain Struct Funct 221:3729-41
Wang, Xiaobo; Olson, Jenessa R; Rasoloson, Dominique et al. (2016) Dynein light chain DLC-1 promotes localization and function of the PUF protein FBF-2 in germline progenitor cells. Development 143:4643-4653
Yi, Feng; DeCan, Evan; Stoll, Kurt et al. (2015) Muscarinic excitation of parvalbumin-positive interneurons contributes to the severity of pilocarpine-induced seizures. Epilepsia 56:297-309
Wilhelm, Márta; Lawrence, J Josh; Gábriel, Robert (2015) Enteric plexuses of two choline-acetyltransferase transgenic mouse lines: chemical neuroanatomy of the fluorescent protein-expressing nerve cells. Brain Res Bull 111:76-83
Thueson, Lindsay E; Emmons, Tiffany R; Browning, Dianna L et al. (2015) In vitro exposure to the herbicide atrazine inhibits T cell activation, proliferation, and cytokine production and significantly increases the frequency of Foxp3+ regulatory T cells. Toxicol Sci 143:418-29
Smith, Michael O; Ball, Jackson; Holloway, Benjamin B et al. (2015) Measuring Aggregation of Events about a Mass Using Spatial Point Pattern Methods. Spat Stat 13:76-89

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