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

 描述（由申请人提供）：端粒长度与寿命和慢性疾病（如心血管疾病和癌症）的风险相关。一个人的端粒长度的相对排名在很大程度上是在出生时确定的，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和疾病的发育起源（DOHaD）的一些观察结果的主要机制候选人，该观察结果将产前事件与慢性疾病的倾向联系起来。出生时端粒长度的增加可能对整个生命过程中的整体健康和慢性疾病易感性产生深远的影响。从怀孕到出生的产前时期特别令人感兴趣，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。这可能使末端限制性片段特别容易受到不利的子宫内条件的影响。令人惊讶的是， 研究已经考虑了子宫内环境对端粒长度的相关性。具体而言，激素因素已被牵连到发挥作用的终端限制片段的侵蚀，表明宫内暴露于内分泌干扰化学品（EDCs）可能会破坏激素信号和端粒的发展。在孕妇和婴儿体内可检测到邻苯二甲酸酯和苯酚的水平，这些化学物质有可能对人类正常的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没有研究过。因此，我们建议使用来自波士顿哈佛医学院布里格姆妇女医院哈佛表观遗传出生队列的样本，确定母体妊娠前三个月尿邻苯二甲酸酯和/或苯酚水平是否与出生时后代的端粒长度相关。

 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.