Abstract

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.

Highlights

  • Proteome of seminal plasma provides profound information related to the male reproductive health

  • Borrachina and collaborators performed a proteomic study in the seminal plasma of infertile patients with normozoospermia, azoospermia, asthenozoospermia and oligoasthenozoospermia and concluded that the current classification of infertile patients based on altered semen parameters resulted in a high heterogeneity in the seminal plasma proteomic profile[30]

  • 48 seminal plasma proteins were identified as DEPs between primary infertility and control group (Table 3)

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Summary

Introduction

Proteome of seminal plasma provides profound information related to the male reproductive health. There is an increased number of reports on seminal plasma proteome to identify potential biomarkers for different pathologies and conditions related to infertility This includes varicocele[13,14,15,16], oxidative stress mediated male infertility[17,18,19,20], nonobstructive azoospermia[21,22,23], asthenozoospermia[24,25], Primary Protein Annexin A2 CD63 CDC42 PRDX2 SEMG1 SEMG2 APP C4. Seminal plasma proteomic study in idiopathic oligoasthenozoospermic men revealed differential expression of proteins such as glycosylated epidydimal secretory protein E1(NPC2), galectin-3-binding protein (M2BP) or lipocalin-1 which provides a basis for further investigations of mechanisms underlying oligoasthenozoospermia[26] These studies provided important information related to mechanisms associated with male infertility, did not provide any evidence on the seminal plasma proteomics based on the type of infertility

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