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

 描述(申请人提供)：端粒长度与长寿有关，并与心血管疾病和癌症等慢性疾病的风险有关。一个人的端粒长度的相对排名在很大程度上是在出生时决定的，随后的端粒侵蚀可能会因环境因素而加剧。这使得端粒长度成为解释健康与疾病发育起源(DOHAD)的一些观察结果的主要机械论候选者，DOHAD将产前事件与慢性病的倾向联系起来。出生时增加的端粒长度可能会对整个生命过程中的整体健康和慢性病易感性产生深远的影响。从受孕到出生的产前阶段特别令人感兴趣，因为这是生命中身体生长最快的阶段，因此加速了细胞的有丝分裂增殖。这可能会使末端限制性片段特别容易受到不利宫内条件的影响。令人惊讶的是，几乎没有人 研究考虑了宫内环境与端粒长度的相关性。具体地说，激素因素被认为在末端限制性片段的侵蚀中发挥了作用，这表明宫内暴露于内分泌干扰物(EDCs)可能会扰乱激素信号和端粒的发育。由于在孕妇和婴儿中检测到邻苯二甲酸盐和酚类的水平，这些化学物质有可能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还没有研究过。因此，我们建议使用波士顿布里格姆妇女医院和哈佛医学院哈佛表观遗传学出生队列的样本来确定母亲怀孕早期尿邻苯二甲酸酯和/或苯酚水平是否与出生时后代的端粒长度有关。

 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.