Altered Molecular Pathways in the Proteome of Cryopreserved Sperm in Testicular Cancer Patients before Treatment
Abstract
:1. Introduction
2. Results
2.1. Semen Parameters
2.2. Sperm Proteome of TC Patients and Normozoospermic Infertile Men
2.3. Biological Pathways Dysregulated in Spermatozoa of Normozoospermic and Asthenozoospermic TC Patients
2.4. Protein Networks and Biofunctions Affected in Asthenozoospermic TC Group
2.5. Western Blot Analysis of Validated DEPs
3. Discussion
4. Materials and Methods
4.1. Study Participants
4.2. Semen Analysis and Cryopreservation
4.3. Sperm Protein Extraction and Quantification
4.4. Liquid Chromatography-Tandem Mass Spectrometry
4.5. Bioinformatic Analysis
4.6. Protein Selection and Validation by Western Blot
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Groups | Canonical Pathways | −log (p-Value) | DEPs |
---|---|---|---|
Normozoospermic TC patients | Phagosome Maturation | 7.19 | DYNC1H1,M6PR,TUBB3,MPO,PRDX1,TUBB4B,TUBA3C/TUBA3D,CANX,ATP6V1A,NAPA |
Sirtuin Signaling Pathway | 6.15 | SLC25A6,PPIF,ATP5F1D,NDUFS7,NDUFA11,CPT1B,TUBA3C/TUBA3D,HIST1H1D,SDHC,SLC25A5,VDAC3,VDAC1 | |
Mitochondrial Dysfunction | 4.67 | ATP5F1D,NDUFA11,NDUFS7,CPT1B,SDHC,OGDH,VDAC1,VDAC3 | |
Atherosclerosis Signaling | 4.61 | ALB,APOB,APOA4,LPL,SERPINA1,COL18A1,CLU | |
Remodeling of Epithelial Adherens Junctions | 3.99 | TUBB3,TUBB4B,TUBA3C/TUBA3D,ACTN4,ACTN1 | |
Asthenozoospermic TC patients | Mitochondrial Dysfunction | 15.7 | HSD17B10,NDUFV1,NDUFS7,ATP5F1A,ATP5PO,ATP5S,VDAC3,UQCRB,VDAC2,PDHA1,ATP5F1C,MTND5,NDUFS1,ATP5F1B,NDUFA11,UQCRC2,NDUFS2,UQCRFS1,GPX4,VDAC1,OGDH |
Oxidative Phosphorylation | 10.9 | NDUFV1,ATP5F1C,MTND5,NDUFS1,ATP5F1B,NDUFS7,NDUFA11,ATP5F1A,UQCRC2,ATP5PO,NDUFS2,UQCRFS1,ATP5S,UQCRB | |
Sirtuin Signaling Pathway | 9.31 | NDUFV1,PPIF,NDUFS7,ATP5F1A,VDAC3,VDAC2,PDHA1,ATP5F1C,NDUFS1,MTND5,ATP5F1B,NDUFA11,UQCRC2,TUBA3C/TUBA3D,NDUFS2,UQCRFS1,VDAC1,SLC25A5,LDHA | |
Protein Ubiquitination Pathway | 6.67 | PSMD7,PSMD13,HSPH1,HSPA9,TRAP1,PSMD3,PSMD8,UCHL3,USP7,PSMC6,PSMD2,DNAJB11,PSMD1,DNAJB1,HSPA4L | |
Phagosome Maturation | 5.3 | DYNC1H1,CTSD,MPO,TUBB4B,CTSB,TUBA3C/TUBA3D,CANX,PRDX6,ATP6V1B2,HLA-DRB5 |
Groups | Normozoospermic TC | Asthenozoospermic TC | ||||
---|---|---|---|---|---|---|
Category | Pathways | p-Value | Number of DEPs | Pathways | p-Value | Number of DEPs |
Disease and disorders | Inflammatory response | 2.36 × 10−14–6.15 × 10−7 | 46 | Inflammatory Response | 1.96 × 10−22–2.37 × 10−3 | 84 |
Cancer | 4.65 × 10−11–7.06 × 10−6 | 142 | Cancer | 3.9 × 10−11–2.19 × 10−3 | 228 | |
Organism injury and abnormalities | 4.65 × 10−11–7.06 × 10−6 | 142 | Organism injury and abnormalities | 3.9 × 10−11–2.39 × 10−3 | 232 | |
Reproductive system disease | 1.3 × 10−10–7.06 × 10−6 | 104 | Metabolic disease | 1.2 × 10−10–2.36 × 10−3 | 90 | |
Neurological disease | 3.21 × 10−10–7.06 × 10−6 | 47 | Gastrointestinal disease | 2.02 × 10−9–2.13 × 10−3 | 214 | |
Molecular and cellular functions | Cellular compromise | 2.36 × 10−14–2.45 × 10−7 | 30 | Cellular compromise | 1.96 × 10−22–1.88 × 10−3 | 59 |
Protein synthesis | 1.06 × 10−11–2.54 × 10−6 | 39 | Protein synthesis | 3.16 × 10−14–2.36 × 10−3 | 74 | |
Post-translational modification | 2.17 × 10−11–6.41 × 10−10 | 18 | Protein degradation | 3.93 × 10−14–2.36 × 10−3 | 39 | |
Protein degradation | 2.17 × 10−11–6.41 × 10−10 | 26 | Cellular assembly and organization | 8.2 × 10−11–2.36 × 10−3 | 46 | |
Lipid metabolism | 4.3 × 10−11–6.79 × 10−6 | 26 | Post-translational modification | 2.08 × 10−10–2.36 × 10−3 | 52 | |
Physiological system development and functions | NA | NA | NA | Reproductive system development and function | 4.14 × 10−10–2.05 × 10−3 | 40 |
NA | NA | NA | Hematological system development and function | 3.85 × 10−7–2.37 × 10−3 | 38 | |
NA | NA | NA | Immune cell trafficking | 3.85 × 10−7–2.37 × 10−3 | 39 | |
NA | NA | NA | Organ development | 9.75 × 10−6–2.4 × 10−3 | 36 | |
NA | NA | NA | Cardiovascular system development and function | 2.62 × 10−5–2.23 × 10−3 | 40 |
Function | p-Value | DEPs |
---|---|---|
Binding of sperm | 4.14 × 10−10 | CCT2,CCT3,CCT5,CCT6A,CCT7,CCT8,PRSS37,SPAM1,TCP1,VDAC2 |
Spermatogenesis | 0.000429 | APOB,ATP1A4,GPX4,H2AFX,HSD17B4,HSPA4L,KIAA1324,NPEPPS,NUP210L,PRSS37 |
Maturation of sperm | 0.00114 | CLU,TPP2 |
Function of sperm | 9.75 × 10−6 | AKAP4,ATP1A4,ATP2B4,PRSS37,SPESP1,VDAC1 |
Cell movement of sperm | 0.000062 | AKAP4,APOB,ATP1A4,ATP2B4,CHDH,GAPDHS,SPAG6,VDAC3 |
Development of genital organ | 0.00205 | ALB,APOB,ATP1A4,GPX4,H2AFX,HSD17B4,HSPA4L,KIAA1324,NPEPPS,NUP210L |
Fertilization | 0.000137 | AKAP3,AKAP4,APOB,ATP1A4,PRSS37,SERPINA5,SPAM1,SPESP1,VDAC1 |
Fertility | 0.000263 | APOB,ATP2B4,CHDH,GPX4,H2AFX,HSD17B4,HSPA4L,LAMB2,LCN2,MMP9 |
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Panner Selvam, M.K.; Agarwal, A.; Pushparaj, P.N. Altered Molecular Pathways in the Proteome of Cryopreserved Sperm in Testicular Cancer Patients before Treatment. Int. J. Mol. Sci. 2019, 20, 677. https://doi.org/10.3390/ijms20030677
Panner Selvam MK, Agarwal A, Pushparaj PN. Altered Molecular Pathways in the Proteome of Cryopreserved Sperm in Testicular Cancer Patients before Treatment. International Journal of Molecular Sciences. 2019; 20(3):677. https://doi.org/10.3390/ijms20030677
Chicago/Turabian StylePanner Selvam, Manesh Kumar, Ashok Agarwal, and Peter N. Pushparaj. 2019. "Altered Molecular Pathways in the Proteome of Cryopreserved Sperm in Testicular Cancer Patients before Treatment" International Journal of Molecular Sciences 20, no. 3: 677. https://doi.org/10.3390/ijms20030677