In utero exposure to endocrine-disrupting chemicals and telomere length at birth

在子宫内接触内分泌干扰化学物质和出生时端粒长度

基本信息

批准号：
8969890
负责人：
KARIN B MICHELS
金额：
$ 8.87万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-06 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8969890
关键词：
Address Affect Age Agonist Benzophenones Birth Body Burden Boston Canned Foods Cardiovascular Diseases Cell Proliferation Centers for Disease Control and Prevention (U.S.)Chemical Exposure Chemicals Child Chromosomes Chronic Disease Complex Conceptions DNA Data Development Disease Disease susceptibility Endocrine Disruptors Environment Environmental Risk Factor Epigenetic Process Epoxy Resins Estradiol Estrogens Event Exposure to First Pregnancy Trimester Genetic Genomics Grouping Growth Growth and Development function Health Hormonal Hormones Hospitals Human Individual Infant Laboratories Length Leukocytes Life Life Cycle Stages Longevity Malignant Neoplasms Measures Mediating Mitosis Mitotic Modeling Molecular Mothers Nature Ovarian Paper Perinatal Exposure Persons Phase Phenols Play Polymers Population Pregnant Women Process Recording of previous events Relative (related person)Risk Role Sampling Signal Transduction Soaps Somatic Cell Steroid biosynthesis Structure Sunscreening Agents Telomere Shortening Time Tissues Toxic effect Triclosan Ultraviolet Rays Umbilical Cord Blood Urine Variant Woman antimicrobial drug bisphenol A cohort consumer product fetal in vivo insight interest medical schools men offspring phthalates polycarbonate plastic prenatal prenatal exposure public health relevance telomere urinary xenoestrogen

项目摘要

DESCRIPTION (provided by applicant): Telomere length is associated with longevity and with the risk for chronic diseases such as cardiovascular disease and cancer. The relative ranking of a person's telomere length is largely determined at birth and subsequent telomeric erosion may be exacerbated by environmental factors. This makes telomere length a prime mechanistic candidate to explain some of the observations of the Developmental Origins of Health and Disease (DOHaD), which connects antenatal events with the propensity of chronic disease. Augmented telomere length at birth may have far-reaching implications with respect to overall health and chronic disease susceptibility throughout the life course. The prenatal period from conception to birth is of particular interest since it is the phase of life marked by the most rapi physical growth and thus accelerated mitotic proliferation of cells. This may make the terminal restriction fragments particularly vulnerable to adverse intrauterine conditions. Surprisingly, few studies have considered the relevance of the intrauterine environment on telomere length. Specifically, hormonal factors have been implicated to play a role in the erosion of the terminal restriction fragments, suggesting that intrauterine exposure to endocrine-disrupting chemicals (EDCs) may disrupt hormonal signaling and telomere development. With detectable levels of phthalates and phenols in pregnant women and infants there is potential for these chemicals to adversely affect normal human growth and development. The impact of prenatal EDC exposure on telomere length has not previously been studied. We therefore propose to determine if maternal first trimester urinary phthalates and/or phenol levels are associated with telomere length of the offspring at birth using samples from the Harvard Epigenetic Birth Cohort at Brigham and Women's Hospital, Harvard Medical School, in Boston.

描述（由适用提供）：端粒长度与寿命和慢性疾病（如心血管疾病和癌症）有关。一个人的端粒长度的相对排名在出生时在很大程度上确定，随后的遥测侵蚀可能会因环境因素而加剧。这使端粒长度成为解释健康和疾病发育起源（DOHAD）的一些观察的主要机械候选者，该观察将产前事件与慢性疾病的希望联系起来。在整个生命过程中，出生时的端粒长度增强可能对整体健康和慢性疾病敏感性具有深远的影响。从概念到出生的产前时期特别令人感兴趣，因为它是生命阶段，其标志性最高的物理生长并因此加速了细胞的有丝分裂增殖。这可能会使末端限制片段特别容易受到不良宫内条件的影响。令人惊讶的是，很少研究已经考虑了内部环境在端粒长度上的相关性。具体而言，已经实施了骑马剂在末端限制片段的侵蚀中发挥作用，这表明内部暴露于内分泌干扰化学物质（EDC）可能会破坏激素信号传导和端粒发育。在孕妇和婴儿中可检测到的邻苯二甲酸盐和苯酚水平，这些化学物质可能会对正常的人类生长和发育产生不利影响。产前EDC暴露对端粒长度的影响以前尚未研究。因此，我们建议使用波士顿波士顿的哈佛大学和女子医院的哈佛表观遗传性出生队列中的样本来确定出生时后代的端粒长度是否与出生时后代的端粒长度有关。