Dietary phytochelatins and their impact on cadmium toxicity in the male reproductive system

膳食植物螯合素及其对男性生殖系统镉毒性的影响

基本信息

批准号：
10389418
负责人：
Zachery Ryan Jarrell
金额：
$ 6.98万
依托单位：
EMORY UNIVERSITY
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：
2022-01-15 至 2023-06-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10389418
关键词：
Address Air Animals Antioxidants Biology Cadmium Cell model Cells Chelating Agents Chronic Complex Couples Cysteine Cystine Data Databases Demographic Factors Diet Dietary Cadmium Dietary intake Disulfides Doctor of Philosophy Domestic Fowls Dose Drug Metabolic Detoxication Electrocardiogram Environment Environmental Exposure Environmental Risk Factor Excretory function Exposure to Fertility Food Foundations Generations Glutathione Glutathione Disulfide Goals Heavy Metals High Pressure Liquid Chromatography Histopathology Human Human body Impairment Inductively Coupled Plasma Mass Spectrometry Intervention Ions Isotope Labeling Liquid substance Lung Male Genital Organs Mammals Measures Mediator of activation protein Metabolic Metabolism Metal exposure Metals Methodology Mus Online Systems Oxidation-Reduction Oxidative Stress Peptides Peroxidases Persons Plants Population Proteins Public Health Reactive Oxygen Species Regulation Reproductive Health Research Resolution Risk Role Route Science Sperm Count Procedure Stress Sulfhydryl Compounds Supplementation System Systems Analysis Techniques Technology Testing Tissues Toxic effect Toxicology Tracer Training Urine Work antioxidant enzyme career career development data repository dietary drinking water enzyme activity epigenomics experience experimental study exposed human population human male human tissue improved interest lifestyle factors male male fertility metabolomics metal chelator metal complex mouse model multiple omics phytochelatin post-doctoral training prevent reproductive reproductive function reproductive organ reproductive tract selenoenzyme sperm cell sperm quality toxicant virtual

项目摘要

PROJECT SUMMARY Male fertility has been on the decline in recent decades, and this is due in part to the large number of environmental exposures humans encounter daily. Among these, the heavy metal, cadmium (Cd), is a notable male reproductive toxicant which is present in the air, drinking water, and numerous components of the diet, and the average person is exposed to 30 µg per day through their diet. Cd is toxic through a number of mechanisms, but much of its effects are caused through generation of oxidative stress and interference with antioxidant defenses. Plant systems deal with toxic Cd and other heavy metal exposures by producing phytochelatins (PyCs), metal chelating peptides with a high thiol content. PyCs are present in virtually any human diet, but their function in the human body is unstudied. The PyC-Cd interactions detailed in plants, along with preliminary findings of PyC in human urine, leads to the hypothesis that dietary PyCs can intervene against dietary Cd in an animal system. This will be tested by use of multiple omics technologies as well as techniques for assessing redox biology and multiple measures of male fertility and reproductive health. Aim 1 will determine the metabolism and distribution of PyCs throughout a murine model by use of high-resolution metabolomics and an isotopically labeled tracer, and the impact of PyC treatment on metal distributions will be determined by use of high-resolution metabolomics and metallomics. Aim 2 will determine the effects of PyC administration alongside Cd exposures in the male reproductive system by analyses of redox potentials and antioxidant enzyme activity as well as a multi-omics (metabolomics, metallomics, and epigenomics) analysis of reproductive tissues alongside assessments of fertility, sperm quality and histopathology. These experiments will generate critical integrative omics of dietary Cd’s impact on the redox systems which protect male reproductive health, and they will result in interventions for improving general and reproductive health in populations strongly impacted by Cd exposures by demonstrating dietary phytochelatins as metal detoxifiers in humans.

项目概要近几十年来，男性生育能力一直在下降，部分原因是大量男性生育人类日常接触的环境暴露中，重金属镉（Cd）是值得注意的。存在于空气、饮用水和饮食的多种成分中的男性生殖毒物，以及一般人每天通过饮食接触 30 微克镉，镉通过多种机制产生毒性。但其大部分影响是通过氧化应激的产生和抗氧化剂的干扰引起的植物系统通过产生植物螯合素来应对有毒的镉和其他重金属暴露。（PyC），具有高硫醇含量的金属螯合肽几乎存在于任何人类饮食中，但它们的含量不同。植物中 PyC-Cd 相互作用的详细信息以及初步研究尚未研究。人类尿液中 PyC 的发现导致了这样的假设：膳食 PyC 可以干预膳食 Cd 这将通过使用多种组学技术以及评估技术进行测试。氧化还原生物学和男性生育力和生殖健康的多项措施将决定。通过使用高分辨率代谢组学和分析方法，研究 PyC 在整个小鼠模型中的代谢和分布同位素标记示踪剂，PyC 处理对金属分布的影响将通过使用来确定目标 2 将确定 PyC 管理的效果以及高分辨率代谢组学和金属组学。通过氧化还原电位和抗氧化酶活性分析确定男性生殖系统中的镉暴露以及生殖组织的多组学（代谢组学、金属组学和表观基因组学）分析这些实验将与生育力、精子质量和组织病理学的评估一起产生重要的结果。膳食镉对保护男性生殖健康的氧化还原系统影响的综合组学，以及它们将采取干预措施改善受镉严重影响的人群的一般健康和生殖健康通过证明膳食植物螯合素作为人类的金属解毒剂来暴露暴露。