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

项目摘要/摘要 酚是一种化学物质，存在于从个人护理产品到食品的众多日常用品中。 包装材料。暴露很普遍，在世界各地的人群中都能检测到尿液水平。研究 已证明酚类物质可作为内分泌干扰物，具有雌激素样、抗雌激素样和抗雄激素样作用。 效果。它们还影响药物代谢酶，这些酶调节人体的排毒过程，以及 正常生殖功能背后的激素代谢和生物利用度。尽管看似有理 酚可能影响女性生殖功能的机制，结果不一致 调查苯酚暴露对生殖影响的有限流行病学研究。在某种程度上，这是 因为酚类物质会迅速代谢和排泄，这使得暴露评估具有挑战性。至 要准确地描述苯酚暴露的特征，重复测量是必要的，但到目前为止，大多数研究都使用 单一衡量标准。这项建议利用了调查问卷和日记数据，以及重复的每日尿液 样本来自221名尝试怀孕的女性的预期队列，这是一项早期怀孕研究。它的目标是 研究接触五种苯酚(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 药物代谢酶中与苯酚相关的潜在变化，从而通过 对尿液代谢物的评估。目标1评估酚的浓度是否与 具有生殖功能。我们将量化苯酚水平与怀孕时间、风险之间的关系 早期妊娠丢失、卵泡期长度和激素水平。在目标2中，我们调查潜力 酚类物质可能具有内分泌干扰作用并改变尿液代谢组的途径 靶向和非靶向代谢组学方法。通过整合成见流行病学， 生物标记物和代谢组学数据与生育结果，这项研究将提供一个暴露组水平的观点如何 生殖功能可能会受到环境暴露的影响。因为不孕不育是一个日益增长的公众 健康关注与重大的身体、情感和经济后果，确定生殖 毒物是迫切需要的。如果酚导致生育率下降，那么将先入为主的使用降至最低 含有苯酚的普通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者提供发展的机会 代谢组学和流行病学方面的高级数据分析和解释技能。在这次团契期间， 耶鲁大学公共卫生学院和NIEHS的多学科导师团队将与申请者合作 实现她在生殖和环境健康方面进行科学研究的长期目标，以及 指导和培训环境健康专业的学生。

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.