Thursday, May 9, 2024
5/9/2024
PROJECT SUMMARY/ABSTRACT Infertility affects about 15% of couples. Ovulatory dysfunction is a primary cause with unclear etiology. Studies have found that certain chemicals are reproductive toxicants and impair female fertility. However, these studies are limited to a small number of known environmental chemicals, and there are major gaps in understanding of the impacts of simultaneous exposures to thousands of chemicals (i.e., the exposome) on ovarian function and female fertility. Thus, there is a critical need to evaluate how complex chemical exposures target reproductive organs, to determine potential biologic pathways of action, and to identify important sources of exposures and their racial/ethnic disparities to inform opportunities for intervention. Research Aims: The proposed research leverages an exposomics approach to evaluate associations between personal care product (PCP) use, chemical exposure biomarkers, ovarian health biomarkers, and female fertility outcomes. Untargeted high- resolution mass spectrometry will measure up to 100,000 chemicals and endogenous metabolites in samples of blood or follicular fluid surrounding developing oocytes. Aim 1 will use machine learning to develop a generalizable database of signatures in the blood exposome that identify PCP habits, based on 4,188 women in the Sister Study. This will create a key resource for other ‘omics health studies to retrospectively assess PCP exposures in banked biologic samples. The PCP signatures can also be used to underpin interpretations of the chemical exposome in Aims 2 and 3. Aim 2 will evaluate associations between the chemical exposome in follicular fluid and fertility (e.g., oocyte yield, clinical pregnancy, and live birth) among 70 women undergoing assisted reproduction technology (ART) from the EMPOWR cohort in Atlanta. Follicular fluid metabolomics will provide mechanistic insights into biologic pathways underlying associations between exposure and outcome. With the racial/ethnic diversity of the cohorts in Aims 1–2, we will also investigate disparities in exposure, PCP signatures, and fertility. Aim 3 will leverage a third cohort of ~250 women in the EARTH study undergoing ART in Massachusetts and will determine associations of PCP habits and the blood and follicular fluid exposomes with fertility, while also providing an independent cohort for evaluating shared biological effects identified in Aim 2. Career Goals: Dr. Anna Young’s background includes strong, cross-disciplinary training in environmental epidemiology, chemical exposure assessment, and computer science. This K99/R00 award will provide critical development of expertise in exposomics, applied data science, and reproductive epidemiology to position her for a high-impact independent research career studying the impact of the exposome on understudied female reproductive disorders. Dr. Young’s training will consist of courses, conferences, seminars, and hands-on mentoring from an exceptional multi-disciplinary team: Drs. Douglas Walker (primary mentor), Audrey Gaskins (co-mentor), Russ Hauser, Chris Gennings, Shruthi Mahalingaiah, Alexandra White, and Christine Ekenga.
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