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Comparative Study
. 2019 Jul 11;10(7):522.
doi: 10.3390/genes10070522.

Sperm Proteome Analysis and Identification of Fertility-Associated Biomarkers in Unexplained Male Infertility

Manesh Kumar Panner Selvam  1 , Ashok Agarwal  2 , Peter Natesan Pushparaj  3   4 , Saradha Baskaran  1 , Hocine Bendou  5
Affiliations
Comparative Study

Sperm Proteome Analysis and Identification of Fertility-Associated Biomarkers in Unexplained Male Infertility

Manesh Kumar Panner Selvam et al. Genes (Basel). .

Abstract

Up to 30% of men with normal semen parameters suffer from infertility and the reason for this is unknown. Altered expression of sperm proteins may be a major cause of infertility in these men. Proteomic profiling was performed on pooled semen samples from eight normozoospermic fertile men and nine normozoospermic infertile men using LC-MS/MS. Furthermore, key differentially expressed proteins (DEPs) related to the fertilization process were selected for validation using Western blotting. A total of 1139 and 1095 proteins were identified in normozoospermic fertile and infertile men, respectively. Of these, 162 proteins were identified as DEPs. The canonical pathway related to free radical scavenging was enriched with upregulated DEPs in normozoospermic infertile men. The proteins associated with reproductive system development and function, and the ubiquitination pathway were underexpressed in normozoospermic infertile men. Western blot analysis revealed the overexpression of annexin A2 (ANXA2) (2.03 fold change; P = 0.0243), and underexpression of sperm surface protein Sp17 (SPA17) (0.37 fold change; P = 0.0205) and serine protease inhibitor (SERPINA5) (0.32 fold change; P = 0.0073) in men with unexplained male infertility (UMI). The global proteomic profile of normozoospermic infertile men is different from that of normozoospermic fertile men. Our data suggests that SPA17, ANXA2, and SERPINA5 may potentially serve as non-invasive protein biomarkers associated with the fertilization process of the spermatozoa in UMI.

Keywords: biomarkers; male infertility; normozoospermic infertile men; sperm proteomics; unexplained male infertility.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Differentially expressed proteins (DEPs) in normozoospermic fertile men and normozoospermic infertile men. UE: underexpressed and OE: overexpressed.
Figure 2
Figure 2
Molecular and cellular functions enriched in the normozoospermic infertile men.
Figure 3
Figure 3
Key canonical pathways enriched in normozoospermic infertile men due to the involvement of overexpressed differentially expressed proteins.
Figure 4
Figure 4
Differentially expressed proteins involved in top networks: (a) cellular compromise, inflammatory response, cell-to-cell signaling, and interaction; (b) organismal injury and abnormalities, cell death, and survival. These non-directional protein networks were generated using IPA.
Figure 5
Figure 5
Protein expression levels of the differentially expressed proteins selected for validation by Western blotting in UMI: normozoospermic infertile men (n = 10) relative to control: normozoospermic fertile men (n = 10). (a) ANXA2 (b) PRDX2, (c) SPA17, and (d) SERPINA5. Results are expressed as mean ±SEM and in fold variation to normozoospermic fertile men. UMI: unexplained male infertility.
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