Alterations in seminal plasma proteomic profile in men with primary and secondary infertility

Proteome of seminal plasma provides profound information related to the male reproductive health. This pilot study was conducted to characterize proteomic profile of seminal plasma from men with primary, or secondary infertility and compare it with proven fertile men. Study participants (n = 59) were recruited at the Cleveland Clinic and divided according to their fertility status: proven fertile (n = 39); primary infertility (n = 11) and secondary infertility (n = 9). Proteomic shotgun analysis revealed a total of 515 peptides common to primary infertility and control group; whereas 523 peptides were common to secondary infertility and control group. Bioinformatic analysis revealed dysregulation of biological processes such as cell secretion and vesicle mediated transport in primary infertility, whereas immune system response, regulation of proteolysis and iron homeostasis were dysregulated in secondary infertility. Western blot validation showed overexpression of ANXA2 and CDC42, and underexpression of SEMG2 proteins in primary infertility; and overexpression of ANXA2 and APP proteins in secondary infertility. This study elucidates the potential role of differentially expressed proteins in the seminal plasma as diagnostic biomarker for primary and secondary infertility. Furthermore, our results suggest maturation failure and immune reaction response as the main cause of infertility in men with primary and secondary infertility, respectively. Additional validation of the proteins involved in the above pathways is warranted.