Exposome Profiling of Environmental Pollutants in Seminal Plasma and Novel Associations with Semen Parameters

Indicators of male fertility are in decline globally,
but the underlying
causes, including the role of environmental exposures, are unclear.
This study aimed to examine organic chemical pollutants in seminal
plasma, including both known priority environmental chemicals and
less studied chemicals, to identify uncharacterized male reproductive
environmental toxicants. Semen samples were collected from 100 individuals
and assessed for sperm concentration, percent motility, and total
motile sperm. Targeted and nontargeted organic pollutant exposures
were measured from seminal plasma using gas chromatography, which
showed widespread detection of organic pollutants in seminal plasma
across all exposure classes. We used principal component pursuit (PCP)
on our targeted panel and derived one component (driven by etriadizole)
associated with total motile sperm (p < 0.001)
and concentration (p = 0.03). This was confirmed
by the exposome-wide association models using individual chemicals,
where etriadizole was negatively associated with total motile sperm
(FDR q = 0.01) and concentration (q = 0.07). Using PCP on 814 nontargeted spectral peaks identified
a component that was associated with total motile sperm (p = 0.001). Bayesian kernel machine regression identified one principal
driver of this association, which was analytically confirmed to be N-nitrosodiethylamine. These findings are promising and
consistent with experimental evidence showing that etridiazole and N-nitrosodiethylamine may be reproductive toxicants.