Organophosphate Esters, Sperm Mitochondrial DNA Copy Number, and Semen Quality: A Longitudinal Study with Repeated Measurements

Toxicological studies revealed that exposure to organophosphate esters (OPEs) affects semen quality, but human evidence is controversial. Over a 3-month follow-up, 1,385 healthy young men provided 3,550 urine samples and 6,466 semen samples, which were determined for urinary OPE metabolite concentrations, sperm quality parameters, and sperm mitochondrial DNA copy number (mtDNAcn). Linear mixed models revealed inverse associations between diphenyl phosphate (DPHP) concentrations and sperm concentration [-3.81% (95% CI: -6.31, -1.24) per each 2-fold increment in exposure], total count [-4.07% (95% CI: -7.21, -0.76)], progressive motility [-0.55 (95% CI: -0.93, -0.17)], and total motility [-0.54 (95% CI: -0.91, -0.17)]; and between bis(2-butoxyethyl) phosphate (BBOEP) and diocresyl phosphate and di-p-cresyl phosphate (DoCP and DpCP) concentrations and sperm concentration [-3.61% (95% CI: -5.53, -1.58) and -3.27% (95% CI: -5.92, -0.48), respectively] and total count [-5.13% (95% CI: -7.53, -2.67) and -3.87% (95% CI: -7.21, -0.35), respectively]. These inverse associations persisted only for DPHP, DoCP and DpCP, and BBOEP measured during the epididymal storage period. Sperm mtDNAcn mediated 67.7% and 52.5%, respectively, of the associations between BBOEP and sperm concentration and total count [beta coefficient of average causal mediation effects = -0.15 (95% CI: -0.25, -0.07) and -0.18 (95% CI: -0.29, -0.08), respectively].