Home LiteratureArticle Details
PMID: 30764484 Published · epublish English Journal Article

Altered Molecular Pathways in the Proteome of Cryopreserved Sperm in Testicular Cancer Patients before Treatment.

International journal of molecular sciences ·Vol. 20 ·No. 3 ·2019-02-05

Panner Selvam MK, Agarwal A, Pushparaj PN

Abstract

Testicular cancer (TC) represents the most common cancer affecting men within the reproductive age and is often accompanied by major disturbances in semen parameters. Cryopreservation is recommended in these patients before initiating cancer treatment. Currently, there are no studies reporting the molecular mechanisms associated with altered semen quality in these men. The main objective of this study was to compare the sperm proteome of normozoospermic (motility >40%) and asthenozoospermic (motility <40%) TC patients with normozoospermic infertile men without cancer (control group). Pooled sperm samples from normozoospermic (n = 20), asthenozoospermic (n = 11) TC, and a control group (n = 9) were used for quantitative global proteomic profiling using liquid chromatography-tandem mass spectrometry. A total of 1085, 846, and 982 proteins were identified in normozoospermic TC, asthenozoospermic TC, and control groups, respectively. Functional analysis revealed mitochondrial dysfunction and altered cellular pathways in both normozoospermic and asthenozoospermic TC patients. Comparison of pathway analysis showed no significant difference in fertility-associated proteins/mechanism between the normozoospermic TC patients and infertile men. Western blot analysis revealed under-expression of NDUFS1 associated with mitochondrial dysfunction and overexpression of CD63 involved in sperm maturation in both normozoospermic and asthenozoospermic TC patients. Our proteomic results confirm that defective cellular pathways are associated with reproductive functions in both normozoospermic and asthenozoospermic TC patients before the start of cancer treatment.

Keywords
cryopreservation proteomics sperm testicular cancer unexplained infertility
MeSH Terms
Adult Asthenozoospermia/metabolism Cryopreservation/methods Humans Infertility, Male/metabolism Male Protein Interaction Maps Proteome/analysis,metabolism Proteomics Semen Analysis Semen Preservation/methods Signal Transduction Sperm Motility Spermatozoa/cytology,metabolism Testicular Neoplasms/metabolism,therapy
Chemicals
Proteome
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Panner Selvam Manesh Kumar
American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. [email protected].
Agarwal Ashok ORCID
American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. [email protected].
Pushparaj Peter N ORCID
Center of Excellence in Genomic Medicine Research, Jeddah 21589, Saudi Arabia. [email protected].
References (65)
65 references, click to expand
  1. Risk of testicular cancer in men with abnormal semen characteristics: cohort study.
    BMJ. 2000 Sep 30;321(7264):789-92 PMID: 11009515
  2. Poor semen quality from patients with malignancies does not rule out sperm banking.
    Urol Res. 2000 Aug;28(4):281-4 PMID: 11011969
  3. Sperm banking and rate of assisted reproduction treatment: insights from a 15-year cryopreservation program for male cancer patients.
    Cancer. 2003 Apr 1;97(7):1624-9 PMID: 12655518
  4. Testicular cancer and Hodgkin's disease: evaluation of semen quality.
    Hum Reprod. 2003 Apr;18(4):796-801 PMID: 12660273
  5. Asthenozoospermia: analysis of a large population.
    Arch Androl. 2003 Sep-Oct;49(5):343-9 PMID: 12893510
  6. Semen parameters in patients with unilateral testicular cancer compared to patients with other malignancies.
    Arch Gynecol Obstet. 2004 Mar;269(3):196-8 PMID: 12898144
  7. Fertility after testicular cancer treatments: results of a large multicenter study.
    Cancer. 2004 Feb 15;100(4):732-7 PMID: 14770428
  8. Sperm proteome mapping of a patient who experienced failed fertilization at IVF reveals altered expression of at least 20 proteins compared with fertile donors: case report.
    Hum Reprod. 2004 Jun;19(6):1438-47 PMID: 15105389
  9. Normal semen parameters in cancer patients presenting for cryopreservation before gonadotoxic therapy.
    Fertil Steril. 2004 Aug;82(2):505-6 PMID: 15302317
  10. Implications of systemic malignancies on human fertility.
    Reprod Biomed Online. 2004 Dec;9(6):673-9 PMID: 15670419
  11. Semen quality before and after gonadotoxic treatment.
    Hum Reprod. 2005 Mar;20(3):774-81 PMID: 15689346
  12. Identification of post-translational modifications that occur during sperm maturation using difference in two-dimensional gel electrophoresis.
    Proteomics. 2005 Mar;5(4):1003-12 PMID: 15712234
  13. Disruption of spermatogenesis by the cancer disease process.
    J Natl Cancer Inst Monogr. 2005;(34):9-12 PMID: 15784813
  14. Spermatogenesis after cancer treatment: damage and recovery.
    J Natl Cancer Inst Monogr. 2005;(34):12-7 PMID: 15784814
  15. Role of exosomes in sperm maturation during the transit along the male reproductive tract.
    Blood Cells Mol Dis. 2005 Jul-Aug;35(1):1-10 PMID: 15893944
  16. Guidelines on testicular cancer.
    Eur Urol. 2005 Dec;48(6):885-94 PMID: 16126333
  17. Sperm banking: use and outcomes in patients treated for testicular cancer.
    BJU Int. 2007 Jan;99(1):33-6 PMID: 17034492
  18. Identification of several proteins involved in regulation of sperm motility by proteomic analysis.
    Fertil Steril. 2007 Feb;87(2):436-8 PMID: 17074334
  19. Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood.
    Hum Reprod. 2008 Jan;23(1):178-86 PMID: 18024486
  20. Identification of proteomic differences in asthenozoospermic sperm samples.
    Hum Reprod. 2008 Apr;23(4):783-91 PMID: 18281682
  21. Proteomics in the study of the sperm cell composition, differentiation and function.
    Syst Biol Reprod Med. 2008 Jan-Feb;54(1):23-36 PMID: 18543863
  22. Trafficking and function of the tetraspanin CD63.
    Exp Cell Res. 2009 May 15;315(9):1584-92 PMID: 18930046
  23. Increased risk of testicular germ cell cancer among infertile men.
    Arch Intern Med. 2009 Feb 23;169(4):351-6 PMID: 19237718
  24. Analysis of proteomic changes associated with sperm capacitation through the combined use of IPG-strip pre-fractionation followed by RP chromatography LC-MS/MS analysis.
    Proteomics. 2010 Feb;10(3):482-95 PMID: 19943266
  25. Proteomics-based study on asthenozoospermia: differential expression of proteasome alpha complex.
    Mol Hum Reprod. 2010 Jul;16(7):452-62 PMID: 20304782
  26. Methodological advances in sperm proteomics.
    Hum Fertil (Camb). 2010 Dec;13(4):263-7 PMID: 21117936
  27. Evaluation of semen quality in patients with malignancies referred for sperm banking before cancer treatment.
    Andrologia. 2011 Oct;43(5):317-20 PMID: 21729127
  28. Proteomic characteristics of spermatozoa in normozoospermic patients with infertility.
    J Proteomics. 2012 Sep 18;75(17):5426-36 PMID: 22771312
  29. The semen quality of 1158 men with testicular cancer at the time of cryopreservation: results of the French National CECOS Network.
    J Androl. 2012 Nov-Dec;33(6):1394-401 PMID: 22837112
  30. Comparative proteomic study between human normal motility sperm and idiopathic asthenozoospermia.
    World J Urol. 2013 Dec;31(6):1395-401 PMID: 23455884
  31. Guidelines for reporting quantitative mass spectrometry based experiments in proteomics.
    J Proteomics. 2013 Dec 16;95:84-8 PMID: 23500130
  32. Proteomic analysis of human spermatozoa proteins with oxidative stress.
    Reprod Biol Endocrinol. 2013 May 20;11:48 PMID: 23688036
  33. Fertility outcome of patients with testicular tumor: before and after treatment.
    Asian J Androl. 2014 Jan-Feb;16(1):107-11 PMID: 24369141
  34. Sperm cryopreservation before testicular cancer treatment and its subsequent utilization for the treatment of infertility.
    ScientificWorldJournal. 2014 Jan 22;2014:575978 PMID: 24587730
  35. High-throughput sperm differential proteomics suggests that epigenetic alterations contribute to failed assisted reproduction.
    Hum Reprod. 2014 Jun;29(6):1225-37 PMID: 24781426
  36. Proteomics, oxidative stress and male infertility.
    Reprod Biomed Online. 2014 Jul;29(1):32-58 PMID: 24813754
  37. Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions.
    Nucleic Acids Res. 2014 Jun;42(11):7290-304 PMID: 24838567
  38. Fertility of testicular cancer patients after anticancer treatment--experience of 11 years.
    Pharmazie. 2014 Jun;69(6):437-41 PMID: 24974577
  39. Identification of proteins involved in human sperm motility using high-throughput differential proteomics.
    J Proteome Res. 2014 Dec 5;13(12):5670-84 PMID: 25250979
  40. Assisted reproductive outcomes of male cancer survivors.
    J Cancer Surviv. 2015 Jun;9(2):208-14 PMID: 25272983
  41. Investigation of male infertility using quantitative comparative proteomics.
    J Proteome Res. 2014 Dec 5;13(12):5403-14 PMID: 25355644
  42. The Association Between Testis Cancer and Semen Abnormalities Before Orchiectomy: A Systematic Review.
    J Adolesc Young Adult Oncol. 2014 Dec 1;3(4):153-159 PMID: 25538860
  43. A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia.
    J Assist Reprod Genet. 2015 Jun;32(6):853-63 PMID: 25825237
  44. Major protein alterations in spermatozoa from infertile men with unilateral varicocele.
    Reprod Biol Endocrinol. 2015 Feb 22;13:8 PMID: 25890347
  45. Impact of precise modulation of reactive oxygen species levels on spermatozoa proteins in infertile men.
    Clin Proteomics. 2015 Feb 09;12(1):4 PMID: 25972767
  46. Infertility with Testicular Cancer.
    Urol Clin North Am. 2015 Aug;42(3):409-20 PMID: 26216827
  47. Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species.
    Clin Proteomics. 2015 Aug 28;12(1):23 PMID: 26321892
  48. Rictor Regulates Spermatogenesis by Controlling Sertoli Cell Cytoskeletal Organization and Cell Polarity in the Mouse Testis.
    Endocrinology. 2015 Nov;156(11):4244-56 PMID: 26360620
  49. Proteomic analysis of mature and immature ejaculated spermatozoa from fertile men.
    Asian J Androl. 2016 Sep-Oct;18(5):735-46 PMID: 26510506
  50. Sperm Proteome Maturation in the Mouse Epididymis.
    PLoS One. 2015 Nov 10;10(11):e0140650 PMID: 26556802
  51. Subfertility increases risk of testicular cancer: evidence from population-based semen samples.
    Fertil Steril. 2016 Feb;105(2):322-8.e1 PMID: 26604070
  52. Reproduction and marriage among male survivors of cancer in childhood, adolescence and young adulthood: a national cohort study.
    Br J Cancer. 2016 Feb 2;114(3):348-56 PMID: 26794280
  53. Semen quality of 4480 young cancer and systemic disease patients: baseline data and clinical considerations.
    Basic Clin Androl. 2016 Feb 18;26:3 PMID: 26893905
  54. Cell penetrating SERPINA5 (ProteinC inhibitor, PCI): More questions than answers.
    Semin Cell Dev Biol. 2017 Feb;62:187-193 PMID: 27989561
  55. Emerging Role for Mammalian Target of Rapamycin in Male Fertility.
    Trends Endocrinol Metab. 2017 Mar;28(3):165-167 PMID: 28063768
  56. Semen quality before cryopreservation and after thawing in 543 patients with testicular cancer.
    JBRA Assist Reprod. 2017 Feb 1;21(1):31-34 PMID: 28333030
  57. Fertility preservation for men with testicular cancer: Is sperm cryopreservation cost effective in the era of assisted reproductive technology?
    Urol Oncol. 2018 Mar;36(3):92.e1-92.e9 PMID: 29169844
  58. Male infertility: a biomarker of individual and familial cancer risk.
    Fertil Steril. 2018 Jan;109(1):6-19 PMID: 29307404
  59. Cancer statistics, 2018.
    CA Cancer J Clin. 2018 Jan;68(1):7-30 PMID: 29313949
  60. A search for molecular mechanisms underlying male idiopathic infertility.
    Reprod Biomed Online. 2018 Mar;36(3):327-339 PMID: 29336995
  61. Proteomic profile of human spermatozoa in healthy and asthenozoospermic individuals.
    Reprod Biol Endocrinol. 2018 Feb 27;16(1):16 PMID: 29482568
  62. Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility.
    J Urol. 2018 Aug;200(2):414-422 PMID: 29530785
  63. The sperm mitochondrion: Organelle of many functions.
    Anim Reprod Sci. 2018 Jul;194:71-80 PMID: 29605167
  64. Differences in semen characteristics between patients with testicular cancer and other malignancies using various cut-off values.
    Int J Urol. 2018 Sep;25(9):817-824 PMID: 29963714
  65. Fatherhood and Sperm DNA Damage in Testicular Cancer Patients.
    Front Endocrinol (Lausanne). 2018 Sep 13;9:506 PMID: 30271379
Article Info
Journal
International journal of molecular sciences
Abbr.
Int J Mol Sci
ISSN
1422-0067
DOI
10.3390/ijms20030677
Email
[email protected]
[email protected]
[email protected]
Published
2019-02-05
Epub
2019-00-05
Language
English
Region
Switzerland
NLM ID
101092791
PMCID
PMC6387327
Subset
IM
External Links
PubMed source DOI: 10.3390/ijms20030677 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2