Non-Targeted Analysis of Environmental Contaminants and Their Associations with Semen Health Factors in Men from New York City

Characterizing the chemical composition of semen can provide valuable insights into the exposome and environmental factors that directly affect seminal and overall health. In this study, we compared molecular profiles of 45 donated semen samples from general population New York City participants and examined the correlation between the chemical profiles in semen and fertility parameters, i.e., sperm concentration, sperm motility, sperm morphology, and semen volume. Samples were prepared using a protein precipitation procedure and analyzed using liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS). Non-targeted analysis (NTA) revealed 18 chemicals not previously reported in human exposome studies, with 3-hydroxyoctanedioic acid, a cosmetic additive, emerging as a plausible candidate found to be at higher levels in cases vs controls (<i>p</i> < 0.01) and associated with adverse sperm motility and morphology. Four level 1 identified compounds were found to have associations with semen health parameters; dibutyl phthalate and 2-aminophenol negatively impacted motility, 4-nitrophenol was associated with low morphology, while palmitic acid was found to be associated with both low morphology and low volume. This study aims to utilize NTA to understand the association of contaminants of emerging concern (CECs) along with a full chemical profile to find trends separating poor and normal semen health parameters from each other chemically. Our results suggest that the collective effects of many CECs could adversely affect semen quality.