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

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