权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

苯酚暴露对生殖功能和尿液代谢组的影响

基本信息

批准号：
10158004
负责人：
Ana Katherine Rosen Vollmar
金额：
$ 3.34万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10158004
关键词：
Affect Attention Attenuated Benzophenones Binding Biological Availability Biological Markers Centers for Disease Control and Prevention (U.S.)Chemicals Cosmetics Data Data Analyses Detoxification Process Emotional Endocrine Disruptors Endocrine disruption Environmental Exposure Environmental Health Enzymes Epidemiology Estrogen Antagonists Estrogens Excretory function Exposure to Fellowship Female Fertility Food Food Packaging Future Goals Health Health Benefit Herbicides Hormones In Vitro Individual Infertility Investigation Length Literature Luteinizing Hormone Measurable Measurement Measures Mediating Menstrual cycle Mentors Metabolic Pathway Metabolism Molecular National Institute of Environmental Health Sciences North Carolina Nuclear Receptors Outcome Outcome Study Parabens Pathway Analysis Pathway interactions Pharmaceutical Preparations Phase Phenols Play Population Pregnancy Progesterone Prospective cohort Public Health Public Health Schools Questionnaires Rattus Recommendation Reproductive Health Research Research Training Risk Risk Estimate Sampling Specimen Students Suggestion Sunscreening Agents Techniques Thyroid Gland Training Urine Woman Work antimicrobial base bisphenol A consumer product diaries drug metabolism early pregnancy early pregnancy loss epidemiology study estrogenic hormone metabolism in vivo individual variation infertility treatment inter-individual variation liquid chromatography mass spectrometry metabolome metabolomics multidisciplinary novel packaging material personal care products proliferative phase Menstrual cycle prospective reproductive reproductive function reproductive hormone reproductive toxicity skills steroid hormone steroid hormone metabolism subfertility time-to-pregnancy tool toxicant urinary

项目摘要

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.

项目总结/文摘