This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Approximately 45 million U.S adults are active smokers. Cigarette smoke consists of more than 4000 chemical compounds including polycylic aromatic hydrocarbons, carbon monoxide, hydrogen cyanide, and arsenic. Nicotine, the primary addictive component of cigarettes, is rapidly metabolized to cotinine with a systemic clearance by day 3 post-withdrawal. Biomarkers of cigarette smoke exposure which are present post-nicotine clearance, and which are peripheral markers of sustained neurotoxicity, are lacking. The emphasis of the first study (April-December 2009) was upon identification of abnormalities in tissue protein and metabolite homeostasis which are mirrored by serum markers of toxicity. In the current proposal (Jan-March 2010), we are establishing whether alcohol exposure induced IUGR is mediated by uterine/placental phosphatide availability. Fetal Alcohol Spectrum Disorders (FASD) affect approximately 1 per 100 live births of which low birth weight (LBW) and developmental delays are most common. In rodent models of FASD, gestational exposure to ethanol induces increased embryo resorption and intrauterine growth restriction (IUGR);persistent neurocognitive and behavioral deficits;as well as a variety of craniofacial malformations including microphthalmia and microcephaly . In FASD models, supplementation with phosphatide precursors [choline or omega-3 long-chain polyunsaturated fatty acids (omega-3 LC-PUFAs;fish oil supplement)] during decidualization/placentation alleviates IUGR. Arachidonic acid availability?an established mediator of successful implantation, decidualization, and fetal growth--is mediated by phosphatide transport/metabolism. In the coming year, we will probe whether maternal alcohol consumption modifies the uterine/placental lipid environment leading to IUGR and LBW. Further we will examine whether maternal nutrient supplementation with LC-PUFAs or choline, which is reported to alleviate LBW, will modify the uterine/placental lipid profiles.
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