Nutritional modulation of fetal susceptibility to lower birth weight in relation to inorganic arsenic (iAs) exposure

与无机砷 (iAs) 暴露相关的胎儿对低出生体重易感性的营养调节

• 批准号: 10386034
• 负责人: Jeliyah Shaquan Clark
• 金额: $ 3.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386034
• 关键词: Address; Adult; Advisory Committees; Arsenic; Arsenicals; Attenuated; Biological; Biological Markers; Birth; Birth Weight; Blood; Carbon; Cells; Chronic Disease; Country; Data; Development; Developmental Toxicant; Disease; Environmental Engineering technology; Environmental Health; Environmental Science; Epidemiology; Excretory function; Exposure to; Fellowship; Fetal Development; Fetal Tissues; Folic Acid; Food; Food Interactions; Gene Expression; Genetic Transcription; Individual; Infant; Infant Mortality; Inflammation; Ingestion; Intake; Knowledge; Linear Regressions; Link; Literature; Low Birth Weight Infant; Malignant Neoplasms; Measures; Mentors; Meta-Analysis; Metabolism; Metals; Methylation; Micronutrients; Modeling; Modification; Molecular; National Research Service Awards; Nutrient; Nutritional; Oxidative Stress; Pathway interactions; Placenta; Plant Roots; Policies; Population Study; Predisposition; Pregnancy; Pregnant Women; Prevention; Public Health; Recommendation; Reporting; Research; Research Personnel; Risk; Risk Factors; S-Adenosylmethionine; Serum; Signal Transduction; Supplementation; Testing; Tissues; Toxic effect; Toxicogenomics; Toxicology; Training; Umbilical Cord Blood; United States National Institutes of Health; Variant; Vitamin B Complex; Weight; Work; World Health Organization; cardiovascular disorder risk; clinical practice; cohort; contaminated drinking water; developmental toxicity; dietary; dietary guidelines; doctoral student; early pregnancy; fetal; fetus cell; fortification; fundamental research; hazard; improved; innovation; long-term sequelae; maternal serum; methyl group; mother nutrition; multiple omics; neonate; nutrition; pre-doctoral; prenatal; prenatal exposure; preventive intervention; protective effect; urinary; Address; Adult; Advisory Committees; Arsenic; Arsenicals; Attenuated; Biological; Biological Markers; Birth; Birth Weight; Blood; Carbon; Cells; Chronic Disease; Country; Data; Development; Developmental Toxicant; Disease; Environmental Engineering technology; Environmental Health; Environmental Science; Epidemiology; Excretory function; Exposure to; Fellowship; Fetal Development; Fetal Tissues; Folic Acid; Food; Food Interactions; Gene Expression; Genetic Transcription; Individual; Infant; Infant Mortality; Inflammation; Ingestion; Intake; Knowledge; Linear Regressions; Link; Literature; Low Birth Weight Infant; Malignant Neoplasms; Measures; Mentors; Meta-Analysis; Metabolism; Metals; Methylation; Micronutrients; Modeling; Modification; Molecular; National Research Service Awards; Nutrient; Nutritional; Oxidative Stress; Pathway interactions; Placenta; Plant Roots; Policies; Population Study; Predisposition; Pregnancy; Pregnant Women; Prevention; Public Health; Recommendation; Reporting; Research; Research Personnel; Risk; Risk Factors; S-Adenosylmethionine; Serum; Signal Transduction; Supplementation; Testing; Tissues; Toxic effect; Toxicogenomics; Toxicology; Training; Umbilical Cord Blood; United States National Institutes of Health; Variant; Vitamin B Complex; Weight; Work; World Health Organization; cardiovascular disorder risk; clinical practice; cohort; contaminated drinking water; developmental toxicity; dietary; dietary guidelines; doctoral student; early pregnancy; fetal; fetus cell; fortification; fundamental research; hazard; improved; innovation; long-term sequelae; maternal serum; methyl group; mother nutrition; multiple omics; neonate; nutrition; pre-doctoral; prenatal; prenatal exposure; preventive intervention; protective effect; urinary

PROJECT ABSTRACT This NIH Ruth L. Kirschstein NRSA Individual Predoctoral Fellowship (F31-Diversity) application seeks to promote the training of Jeliyah Clark, a pre-doctoral student in the Department of Environmental Sciences and Engineering at UNC Chapel Hill. Ms. Clark intends to become an independent academic investigator and will receive guidance from her sponsors, Drs. Rebecca Fry and Carmen Marsit, leaders in environmental health; advisory committee, Drs. Alex Keil, Julia Rager, and Mirek Styblo, experts in epidemiology, toxicology, and nutrition, respectively; and mentor, Dr. Chantel Martin, expert in epidemiology. Given widespread inorganic arsenic (iAs) contamination of drinking water, the proposed research will assess nutritional modification of fetal susceptibility to iAs-associated decreases in birth weight. Exposure to iAs during pregnancy is a major public health concern because iAs is a potent developmental toxicant, with several studies linking prenatal exposure to lower birth weight. iAs is also associated with transcriptional dysregulation promoting oxidative stress, inflammation, and other development-related signaling in fetal cells, representing a potential biological mechanism. Notably, iAs metabolism is dependent on folate and other B vitamins comprising the one-carbon metabolism pathway, and B vitamin supplementation has been shown to reduce iAs toxicity. However, iAs- nutrient interactions remain understudied in relation to fetal development, representing a critical barrier to low birth weight prevention. The central hypothesis of this research is that maternal diet modifies fetal susceptibility to iAs-associated decreases in birth weight. In Aim 1, Ms. Clark will determine whether the negative association between iAs exposure and infant BW is modified by maternal serum concentrations of OCM factors. In Aim 2, she will assess whether OCM factors attenuate the positive association between iAs exposure and expression of genes promoting oxidative stress imbalance and inflammation in cord blood. The proposed research will leverage data from an existing pregnancy cohort, the Biomarkers of Exposure to Arsenic (BEAR) cohort (N=200). Likelihood ratio tests of nested linear regression models will be employed to evaluate effect modification of the association between iAs exposure and birth weight (Aim 1) and gene expression in cord blood (Aim 2) by one- carbon metabolism factors. Additionally, data collected from a replication pregnancy cohort will be utilized to validate findings in Aim 1. This research is innovative, as few studies evaluating B vitamins as determinants of maternal iAs methylation efficiency also integrate birth weight and multi-omics assessments that may portend decreased iAs toxicity at the molecular level. The research will have a significant impact, as it explores maternal diet as a preventative intervention for iAs-associated lower birth weight and may inform food fortification policy and dietary recommendations for pregnant women, improving clinical practice.

项目摘要 Nih Ruth L. Kirschstein NRSA个人奖学金（F31多样性）的应用程序寻求 促进对环境科学系的博士前学生Jeliyah Clark的培训， 在UNC Chapel Hill的工程。克拉克女士打算成为一名独立的学术研究员，并将 收到她的赞助商Drs的指导。丽贝卡·弗莱（Rebecca Fry）和卡门·马西特（Carmen Marsit），环境卫生领导者； 咨询委员会博士。亚历克斯·凯尔（Alex Keil），朱莉娅·拉格（Julia Rager）和米雷克·斯泰布洛（Mirek Styblo），流行病学，毒理学和 营养分别；和导师，流行病学专家Chantel Martin博士。给定广泛的无机 饮用水砷（IAS）污染，拟议的研究将评估胎儿的营养修饰 与IAS相关的敏感性减少了出生体重。怀孕期间接触IAS是主要的公众 健康关注，因为IAS是一种有效的发展性毒物，有几项研究将产前暴露与 降低出生体重。 IAS还与转录失调促进氧化应激有关， 胎儿细胞中的炎症和其他与发育相关的信号传导，代表潜在的生物学 机制。值得注意的是，IAS代谢取决于叶酸和其他B族维生素，其中包括单碳 已证明代谢途径和B维生素补充剂可降低IAS毒性。但是，ias- 与胎儿发育有关的营养相互作用仍在研究 预防出生体重。这项研究的中心假设是，孕产妇饮食修饰了胎儿的敏感性 与IAS相关的出生体重降低。在AIM 1中，克拉克女士将确定负面的关联是否 在IAS暴露和婴儿BW之间，OCM因子的母性血清浓度可以改变。在AIM 2中， 她将评估OCM因素是否减弱IAS暴露与表达之间的正相关 促进绳索血液中氧化应激失调和炎症的基因。拟议的研究将 利用现有妊娠队列的数据，即暴露于砷（熊）队列的生物标志物（n = 200）。 将采用嵌套线性回归模型的似然比测试来评估效应的修改 IAS暴露与出生体重（AIM 1）与脐带血中的基因表达之间的关联（AIM 2） 碳代谢因素。此外，将利用从复制妊娠队列中收集的数据 在AIM 1中验证发现。这项研究具有创新性，因为很少有评估B族维生素作为决定因素的研究 孕产妇IAS甲基化效率还整合了可能预期的出生体重和多摩学评估 IAS毒性在分子水平下降低。这项研究将产生重大影响，因为它探索了母亲 饮食作为与IAS相关的较低出生体重的预防干预措施，并可能为食物防御政策提供信息 以及针对孕妇的饮食建议，改善临床实践。