O-247 Seminal Plasma Exposomics and Male Reproductive Parameters
Authors: Machtinger R , Kalia V , Orvieto R , Levine H , Baccarelli A.A , Hoffmann-Dishon N , Aizer A , Pennell K.D , Manz K , Wu H 
Published: June 2022

Abstract

Study question
What novel environmental exposures found in seminal plasma, as individual metabolites and concurrent exposure patterns, are associated with poor male reproductive parameters?

Summary answer
Seminal plasma levels of etridiazole, diethyl phthalate, and polycyclic aromatic hydrocarbons (PAHs) are negatively associated with semen parameters.

What is known already
Numerous environmental exposures have been linked to poor male reproductive markers, but they have typically examined only a limited set of exposures in the urine, which may not be accurate representation of the chemical burden in tissue and do not holistically consider a large range of potential concurrent exposures.

Study design, size, duration
This cross-sectional study included 100 heterosexual couples undergoing assisted reproductive treatment at a Tertiary University Affiliated Medical Center. Semen samples were collected and fractionated to separate sperm (outcome measurement) and seminal plasma (exposomics analysis).

Participants/materials, setting, methods
Semen parameters were assessed for sperm concentration (millions/mL), percent motility, and total motile sperm (millions/mL). Using a novel QuEChERS (quick, easy, cheap, efficient, rugged, and safe) based extraction method, targeted and untargeted organic pollutant exposures were measured from 500uL of seminal plasma using a Thermo Q Exactive Orbitrap mass spectrometer. We used linear regression, principal component pursuit (PCP), and Bayesian Kernel Machine Regression (BKMR) to estimate the associations of organic pollutants with semen parameters.

Main results and the role of chance
We identified 118 known chemicals in seminal plasma from the targeted panel of organic pollutants. Using an exposome-wide association approach, we modeled each exposure with the outcome individually and found that etriadizole, a common pesticide, was negatively associated with total motile sperm (p &lt; 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) in linear regression models. BKMR results confirmed that as an overall mixture, these four pollutants were negatively associated with percent motility, although anthracene was not an important component of the mixture effect. Furthermore, BKMR models showed that other PAHs did not confound or modify the impact of diethyl phthalate, pyrene, and phenanthrene.

Limitations, reasons for caution
Our sample only included 100 men and larger studies are necessary to confirm the associations identified by this investigation. Furthermore, this current analysis only included a limited number of targeted chemicals and future studies should examine untargeted features as well.

Wider implications of the findings
To our knowledge, our study is the first to assess a large set of seminal plasma exposures and their relation to semen parameters. Although the biological mechanism(s) underlying the observed associations are unknown, we identified novel associations. Thus, future investigations using broad exposomic approaches in seminal plasma is warranted.

Trial registration number
PGA 2102 Environmental Health Fund Israel