Multi-matrix chemical exposome characterization and its association with semen quality

Abstract

There is strong evidence to suggest that the chemical exposome may have an impact on human spermatogenesis, contributing to the male fertility decline observed during the last decades. The present study was aimed at identifying the presence of organic chemicals in human seminal plasma, blood plasma and urine, and explore their associations with seminal quality parameters. We applied a novel LC-HRMS based chemical profiling approach for screening more than 2000 organic chemicals in these biofluids from participants (n = 48) to the Spanish Led-Fertyl cohort. The results showed that 42, 42 and 48 chemicals were respectively detected in at least one sample of seminal plasma, urine, and blood plasma, respectively. These co-exposure mixtures included artificial sweeteners, biocides, flame retardants, food-related compounds, PFAS, pharmaceuticals and biomarkers of tobacco exposure. Up to 26 chemicals were detected in all three matrices with positive correlations between them. In turn, our results highlight seminal plasma as a valuable matrix for exposure assessment, as certain chemicals were detected exclusively in this biospecimen, while others—although also present in blood plasma and urine—reached their highest concentrations in seminal plasma. Statistical analyses revealed negative associations between several lesser-studied chemicals—such as 1,3-Dicyclohexylurea, propylparaben, bisphenol S or the biocide nitenpyram—and multiple semen quality parameters. In addition, our approach also confirmed the known negative associations with PFAS and smoking-related compounds, including nicotine and cotinine. This study underscores the potential of wide-scope targeted approaches in epidemiological research, providing valuable insights into the complex interplay between chemical exposures and reproductive health.