Reproductive
Prediction of endometrial tissue PFAS levels using serum biomarkers and demographic and reproductive factors: findings from the Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) Study Anna Z. Pollack* Maggie Fuzak Dr. Helen Chin Dr. Jenna R. Krall Vimalkumar Krishnamoorthi Kurunthachalam Kannan
Exposure to perfluoroalkyl substances (PFAS) is associated with adverse health outcomes. The IMPLANT Study measured PFAS in both serum and endometrium. Endometrium tissue is challenging to obtain and requires invasive surgical procedures. However, measurement of target tissue concentrations of PFAS is more relevant from toxicological point of view. This study aimed to develop prediction models to estimate PFAS concentrations in endometrial tissue based on serum concentrations, demographic characteristics, and reproductive factors
Using data from the operative cohort of the Endometriosis Natural History Diagnosis and Outcomes Study (N=433), which enrolled women undergoing laparoscopy or laparotomy for any indication who were not previously diagnosed with endometriosis, we developed multivariable linear regression and LASSO regression models. Predictor variables included serum PFAS concentrations (e.g., PFOS, PFOA, PFNA), age, BMI, parity, smoking, and menstrual status. The analysis focused on PFOS, PFHpA, PFOA, PFNA, PFDA, PFUnDA, and PFDoDA. Extreme outliers were removed based on the interquartile range (IQR) before analysis. Following these adjustments, the number of participants varied across models depending on the availability of complete data for each PFAS.
Serum PFAS concentrations were the strongest predictors of endometrial tissue levels, particularly for PFOS (R2=0.49; RMSE=3.02). Age and household income contributed to improved predictions for PFUnDA (R2=0.21;RMSE=0.09). However, moderate R-squared values across most PFAS (0.10-0.49) suggest that serum levels only partially predict eutopic tissue concentrations. This highlights that alternative approaches are necessary to better understand PFAS in eutopic tissue.