Characterization of Chemical Exposome in A Paired Human Preconception Pilot Study

Parental preconception exposure to synthetic chemicals may have critical influences on fertility and reproduction. Here, we present a robust LC-MS/MS method covering up to 95 diverse xenobiotics in human urine, serum, seminal and follicular fluids to support exposome-wide assessment in reproductive health outcomes. Extraction recoveries of validated analytes ranged from 62% to 137% and limits of quantification from 0.01 to 6.0 ng/mL in all biofluids. We applied the validated method to a preconception cohort of Australian couples (<i>n</i> = 30) receiving fertility treatment. In total, 36 and 38 xenobiotics were detected across the paired biofluids of males and females, respectively, including PFAS, parabens, organic UV-filters, plastic additives, antimicrobials, and other industrial chemicals. Results showed 39% of analytes in males and 37% in females were equally detected in paired serum, urine, and reproductive fluids. The first detection of the sunscreen ingredient avobenzone and the industrial chemical 4-nitrophenol in follicular and seminal fluids suggests they can cross both blood-follicle/testis barriers, indicating potential risks for fertility. Further, the blood-follicle transfer of perfluorobutanoic acid, PFOA, PFHxS, PFOS, and oxybenzone corroborate that serum concentrations can be reliable proxies for assessing exposure within the ovarian microenvironment. In conclusion, we observed significant preconception exposure to multiple endocrine disruptors in couples and identified potential xenobiotics relevant to male and female fertility impairments.