The effect of phenol exposure on reproductive function and the urinary metabolome

项目总结/摘要 苯酚是一种存在于从个人护理产品到食品等众多日常用品中的化学物质 包装材料。接触是广泛的，在世界各地的人群中可检测到尿液水平。研究 已经表明酚类可以作为内分泌干扰物，具有雌激素、抗雌激素和抗雄激素的作用。 方面的影响.它们还影响介导身体解毒过程的药物代谢酶， 激素代谢和生物利用度是正常生殖功能的基础。尽管似是而非 酚类物质可能影响女性生殖功能的机制，在不同的研究中，结果不一致。 有限的流行病学研究检查苯酚暴露对生殖的影响。这部分是 因为酚类物质代谢和排泄迅速，使接触评估具有挑战性。到 为了准确地描述苯酚暴露，重复测量是必要的，但迄今为止的大多数研究使用的是 一次测量。该提案利用问卷调查和日记数据，沿着重复的每日尿液 样本，从一个前瞻性队列的221名妇女试图怀孕，早孕研究。旨在 检查暴露于五种酚（二苯甲酮-3，对羟基苯甲酸甲酯，对羟基苯甲酸丙酯， 2，4-二氯苯酚和2，5-二氯苯酚）和一系列生殖功能指标，并调查 药物代谢酶的潜在苯酚相关变化，因此激素代谢，通过 尿代谢组学的评估。目的1评价酚类物质的浓度是否与 具有生殖功能。我们将量化苯酚水平与怀孕时间、风险 早期妊娠丢失，卵泡期长度和激素水平。在目标2中，我们研究潜在的 酚类物质可能具有内分泌干扰作用并改变尿代谢组的途径 靶向和非靶向代谢组学方法。通过整合孕前流行病学， 生物标志物和代谢组学数据与生育结果，这项研究将提供一个麻烦的水平，如何 生殖功能可能受到环境暴露的影响。因为不孕症是一个越来越多的公众 健康问题与重大的身体，情感和经济后果，确定生殖 有毒物质是迫切需要的。如果酚类导致生育力下降，那么尽量减少孕前使用 普通的含酚消费品的使用可能对公众健康有很大的好处。完成 这项为期两年的研究和培训奖学金将为申请人提供发展的机会 在代谢组学和流行病学方面具有先进的数据分析和解释技能。在这个奖学金期间， 耶鲁大学公共卫生学院和NIEHS的多学科导师团队将与申请人合作 实现她在生殖健康和环境健康方面进行科学研究的长期目标， 指导和培训环境卫生学生。

Project Summary/Abstract Phenols are chemicals found in numerous everyday items ranging from personal care products to food packaging materials. Exposure is widespread, with detectable urinary levels in populations worldwide. Studies have shown that phenols can act as endocrine disruptors, with estrogenic, antiestrogenic, and antiandrogenic effects. They also impact drug metabolizing enzymes which mediate the body’s detoxification processes, and hormone metabolism and bioavailability underlying normal reproductive function. Despite plausible mechanisms by which phenols could impact female reproductive function, there are inconsistent results across the limited epidemiologic studies examining the reproductive effects of phenol exposure. In part, this is because phenols are rapidly metabolized and excreted, making exposure assessment challenging. To accurately characterize phenol exposure, repeated measures are necessary, but most studies to-date use a single measure. This proposal leverages questionnaire and diary data, along with repeated daily urine samples, from a prospective cohort of 221 women attempting pregnancy, the Early Pregnancy Study. It aims to examine the relationship between exposure to five phenols (benzophenone-3, methyl paraben, propyl paraben, 2,4-dichlorophenol, and 2,5-dichlorophenol) and a range of reproductive function indicators, and to investigate potential phenol-associated changes in drug metabolizing enzymes, and hence hormone metabolism, through assessment of the urinary metabolome. Aim 1 evaluates whether concentrations of phenols are associated with reproductive function. We will quantify the associations between phenol levels and time to pregnancy, risk of early pregnancy loss, follicular phase length, and hormone levels. In Aim 2, we investigate potential pathways by which phenols may have endocrine disrupting effects and alter the urinary metabolome using both targeted and untargeted metabolomics approaches. By integrating preconception epidemiologic, biomarker, and metabolomics data with fertility outcomes, this study will offer an exposome-level view into how reproductive function may be affected by environmental exposures. Because infertility is a growing public health concern with major physical, emotional, and financial consequences, the identification of reproductive toxicants is urgently needed. If phenols contribute to decreased fertility, then minimizing the preconception use of common phenol-containing consumer products could have substantial public health benefits. Completion of this two-year research and training fellowship will provide the applicant with the opportunity to develop advanced data analysis and interpretation skills in both metabolomics and epidemiology. During this fellowship, a multi-disciplinary team of mentors at the Yale School of Public Health and NIEHS will work with the applicant towards her long-term goal of conducting scientific research in reproductive and environmental health, and mentor and train environmental health students.