Pubertal urinary phthalate metabolite concentrations and semen quality among young Russian men: exploring potential windows of susceptibility.

Abstract

Aim: To prospectively investigate the associations of urinary phthalate metabolite concentrations measured during four peri-pubertal windows with semen parameters in Russian men. Methods: 516 boys were enrolled at ages 8-9 years (2003-2005). Urine samples were collected annually and pooled into four pubertal exposure windows based on physician assessed Tanner stages and testicular volume (prepuberty, early puberty, late puberty and sexual maturity). 15 phthalate metabolites were quantified using isotope dilution HPLC-MS/MS at Moscow State University. We calculated molar sums (∑) of di-2-ethylhexyl phthalate (DEHP), non-DEHP, di-isononyl phthalate (DiNP) and di-isodecyl phthalate (DiDP) metabolites. At sexual maturity (18-19 years), men provided 1-2 semen samples for analysis. We estimated the associations between quintiles of ∑phthalate metabolites and semen parameters for each pubertal window by fitting generalized linear mixed models with random intercepts to account for repeated semen samples, adjusting for abstinence time, body mass index, and specific gravity. We also modelled the probability of having a semen sample below any WHO cut-offs measured as <15mil/mL for concentration, <39mil for count, or <32% progressive motility. Results: Higher urinary concentrations of ∑DiNP in the late pubertal samples were associated with poorer semen quality; men with the highest versus lowest quintile of ∑DiNP had 32% lower sperm concentration (p-trend=0.07), 34% lower count (p-trend=0.06) and 33% lower progressive motile count (p-trend=0.09). Also, men with the highest versus lowest quintile of ∑DiNP had 15% higher probability of having a semen parameter below WHO cut-offs (p-trend=0.04). ∑DiNP measured in the other three peri-pubertal windows was not associated with semen quality. No associations of ∑DEHP, ∑non-DEHP and ∑DiDP with semen quality parameters were observed. Conclusions: ∑DiNP metabolites in late puberty was associated with poorer semen quality, highlighting the importance of considering specific windows of exposure when investigating chemical exposures in relation to fertility in men. Funding: NIEHS R01ES0014370 and P30ES000002.