Exposomic Analysis of Organic Pollutants in Seminal Plasma and Male Reproductive Parameters

Previous studies of environmental exposures and male reproductive health have typically examined limited sets of exposures in the urine, which may not accurately capture the chemical burden in relevant tissues and do not consider a large range of concurrent exposures. Here, we used a combined targeted and untargeted exposome approach to identify novel associations of environmental pollutants found in seminal plasma, as individual metabolites and co-exposure patterns, with male reproductive parameters. Semen samples were collected from male partners from 100 heterosexual couples undergoing assisted reproductive treatment in Tel Aviv after 2-7 day abstinence. Semen parameters were assessed for sperm concentration, percent motility, and total motile sperm. Using a novel QuEChERS (quick, easy, cheap, efficient, rugged, and safe) extraction method, 118 targeted and 2005 untargeted organic pollutant exposures were measured from seminal plasma using gas chromatography. We used linear regression, principal component pursuit (PCP), and Bayesian Kernel Machine Regression (BKMR) to estimate the associations of organic pollutants with semen parameters. Using an exposome-wide association approach, we found that etriadizole, a common pesticide, was negatively associated with total motile sperm (p<0.001), concentration (p=0.002), and percent motility (p=0.04). Using PCP, a machine learning pattern recognition approach, we derived a low-rank matrix with one major principal component. This principal component was primarily loaded by one phthalate (diethyl phthalate) and three PAHs (anthracene, pyrene, phenanthrene) and was associated with lower total sperm (p=0.03) and percent motility (p=0.05). BKMR results confirmed that as an overall mixture, these four pollutants were negatively associated with percent motility, although anthracene was not important to the mixture effect. Seminal plasma levels of etridiazole, diethyl phthalate, and polycyclic aromatic hydrocarbons (PAHs) are negatively associated with semen parameters. Future exposomic investigations using seminal plasma are warranted. Keywords: exposomics; exposome; seminal plasma; reproduction; reproductive health; semen; sperm; pesticide, etridiazole, phthalates, PAH