Comparative analysis of interindividual variations in the seminal plasma proteome of fertile men with identification of potential markers for azoospermia in infertile patients.

Seminal plasma is a potential source of biomarkers for many disorders of the male reproductive system. The identification and characterization of proteins in the seminal plasma by using two-dimensional (2-D) difference gel electrophoresis (DIGE) serve as a basis for estimating male infertility. However, individual variation remains an impediment to identifying disease-associated proteins. Therefore, it is necessary to examine the interindividual variations in the seminal plasma proteome of fertile men. The present study analyzed seminal plasma samples from 10 fertile men. The results from silver-stained 2-D DIGE were averaged to reduce gel to gel variations. Up to 501 spots (polypeptides) were detected on the averaged gels for the fertile men. The coefficient of variation (CV) of standardized abundance was calculated for 63 spots that were common to all 10 samples; the CV values ranged from 24.5% to 129.9% with a median value of 63.1%. These results demonstrate that the variability in protein expression among different fertile men is relatively high in seminal plasma compared with that in other human tissue samples. The 63 matched spots were compared with those from 10 patients with azoospermia. There was no common spot that was lost in all of the 10 patients, and 16 of these spots (25%) were present in each of the patients. We identified 4 and 1 candidate markers for nonobstructive and obstructive azoospermia, respectively. These results validate our method of identifying differences in the proteomic profiles of seminal plasma samples and provide an important basis for protein expression profiling and comparative proteomics of infertility.