Exposure to drinking-water disinfection byproducts, seminal plasma metabolomic signatures, and semen quality: Findings from the TREE cohort

Disinfection byproducts (DBPs) have been linked to reduced semen quality, yet the underlying mechanisms are largely unclear. We investigated seminal plasma metabolomic signatures of exposure to DBPs and semen quality and further explored their mediating roles in associations linking exposure to DBPs with semen quality. Untargeted metabolomics analysis and Metabolome-Wide Association Studies (MWAS) were employed to characterize seminal plasma metabolites of DBP exposures and semen quality parameters among 193 participants from the Tongji Reproductive and Environmental (TREE) cohort. Urinary biomarkers of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were assessed as drinking-water DBP exposures. Negative associations between urinary DCAA concentration and sperm total motility and progressive motility were observed. Among the 812 annotated metabolites, urinary DCAA and TCAA concentrations were separately linked with 28 and 24 metabolites, which were primarily involved in arginine and proline metabolism pathway. Additionally, 232 metabolites were related with semen quality parameters, mainly participating in arginine and proline, aspartate and glutamate, arachidonic acid, alanine, and D-amino acid metabolism pathways. Mediation analyses revealed that phosphatidylinositol [PI(18:1/22:6)] mediated the associations between urinary DCAA concentration and reduced sperm progressive motility and total motility, with the mediating effects of 34% and 31%, respectively. Our findings provide novel insights into potential biomarkers of exposure to DBPs and semen quality and enhance understanding of the biological mechanisms through which DBP exposures exert adverse effects on semen quality. • Seminal plasma metabolomic signatures of DBP exposures were firstly examined. • Urinary DCAA and TCAA were separately linked with 28 and 24 metabolites. • 232 metabolites were associated with semen quality parameters. • PI(18:1/22:6) mediated negative associations between urinary DCAA and sperm motility.