Identifying windows of susceptibility to essential elements for semen quality among 1428 healthy men screened as potential sperm donors

Abstract

Background: Essential elements such as iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), strontium (Sr), and molybdenum (Mo) are necessary for reproductive health. However, their associations with human semen quality remain inconclusive.

Objectives: To investigate the associations of urinary Fe, Co, Cu, Zn, Se, Rb, Sr, and Mo concentrations with semen quality in healthy men screened as potential sperm donors and identify critical windows of susceptibility.

Methods: 1428 healthy men provided 3766 urine and 6527 semen samples, which were measured for urinary essential element concentrations and sperm quality parameters, respectively. Linear mixed models and cubic spline curves were used to evaluate associations between urinary essential elements and semen quality. Multiple informant models were used to identify potential critical windows of susceptibility.

Results: Linear mixed models and cubic spline curves showed positive dose-response relationships between urinary Zn and sperm concentration and total count and between urinary Mo and total sperm count [all False Discovery Rate (FDR) adjusted p-value for trend < 0.05]. In the multiple-element linear mixed models, the men in the highest versus lowest quartiles of urinary Zn and Mo had a higher sperm concentration of 17.5% (95% CI: 2.8%, 34.2%; p-value for trend = 0.006) and total sperm count of 18.3% (95% CI: 1.4%, 38.0%; p-value for trend = 0.027), respectively. Urinary Zn was also positively associated with total sperm count in a dose-dependent manner (p-value for trend = 0.036), though the percentile difference in total sperm count between men in the highest and lowest quartile was not statistically significant (16.4%, 95% CI: -1.7%, 37.9%). These associations appeared to be stronger when urinary Zn and Mo were measured at 0-9 days before the date of semen examination (i.e., corresponding to epididymal storage).

Conclusions: Higher urinary Zn and Mo, particularly during the period of epididymal storage, were associated with greater sperm production.

Keywords: Critical window; Essential elements; Repeated measurements; Semen quality; Sperm donors.