Characterization\nof Chemical Exposome in A Paired\nHuman Preconception Pilot Study

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