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

基本信息

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
项目类别：
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

项目摘要

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 个人博士前奖学金（F31-多样性）申请旨在促进环境科学系博士前学生 Jeliah Clark 的培训北卡罗来纳大学教堂山分校的工程学。克拉克女士打算成为一名独立的学术研究者，并将接受她的赞助商博士的指导。丽贝卡·弗莱 (Rebecca Fry) 和卡门·马斯特 (Carmen Marsit)，环境健康领域的领导者；顾问委员会，博士。 Alex Keil、Julia Rager 和 Mirek Styblo 是流行病学、毒理学和营养分别；导师是流行病学专家 Chantel Martin 博士。鉴于广泛存在的无机物饮用水砷（iAs）污染，拟议的研究将评估胎儿的营养调整对 iAs 相关的出生体重下降的易感性。怀孕期间接触 iAs 是一个主要公众健康问题，因为 iAs 是一种强效的发育毒物，多项研究将产前暴露与出生体重较低。 iAs 还与促进氧化应激的转录失调有关，胎儿细胞中的炎症和其他发育相关信号，代表了潜在的生物学机制。值得注意的是，iAs 代谢依赖于叶酸和其他包含一碳维生素的 B 族维生素代谢途径，补充 B 族维生素已被证明可以降低 iAs 毒性。然而，iAs- 营养相互作用与胎儿发育的关系仍未得到充分研究，这是低生育率的一个关键障碍出生体重预防。这项研究的中心假设是母亲的饮食会改变胎儿的易感性与 iAs 相关的出生体重下降。在目标 1 中，克拉克女士将确定负面关联是否 iAs 暴露与婴儿体重之间的关系受 OCM 因子母体血清浓度的影响。在目标 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性促进脐带血氧化应激失衡和炎症的基因。拟议的研究将利用现有妊娠队列、砷暴露生物标志物 (BEAR) 队列 (N=200) 的数据。将采用嵌套线性回归模型的似然比检验来评估修改的效果 iAs 暴露与出生体重（目标 1）和脐带血基因表达（目标 2）之间的关联碳代谢因素。此外，从复制妊娠队列收集的数据将用于验证目标 1 中的发现。这项研究具有创新性，因为很少有研究评估 B 族维生素作为母体 iAs 甲基化效率还整合了出生体重和多组学评估，这可能预示着在分子水平上降低 iAs 毒性。这项研究将产生重大影响，因为它探讨了母亲饮食作为 iAs 相关低出生体重的预防性干预措施，并可能为食品强化政策提供信息以及孕妇饮食建议，改善临床实践。