World J Mens Health.  2020 Apr;38(2):198-207. 10.5534/wjmh.180099.

New Insights on the Mechanisms Affecting Fertility in Men with Non-Seminoma Testicular Cancer before Cancer Therapy

Affiliations
  • 1American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA. agarwaa@ccf.org
  • 2Universidade da Beira Interior, Covilhã, Portugal.
  • 3Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar and Unit for Multidisciplinary Research in Biomedicine, University of Porto, Porto, Portugal.
  • 4Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, Jeddah, Saudi Arabia.
  • 5Division of Pathology, School of Medical Sciences, Sydney University, Sydney, Australia.

Abstract

PURPOSE
Patients with non-seminoma testicular cancer (NSTC) cancer can be subfertile or infertile, and present reduced sperm quality, but the underlying mechanisms are unknown. The aim of this study was to compare the sperm proteome of patients with NSTC, who cryopreserved their sperm before starting cancer treatment, with that from healthy fertile men.
MATERIALS AND METHODS
Semen volume, sperm motility and sperm concentration were evaluated before the cryopreservation of samples from patients with NSTC (n=15) and the control group (n=15). Sperm proteomic analysis was performed by liquid chromatography-tandem mass spectrometry and the differentially expressed proteins (DEPs) between the two groups were identified using bioinformatic tools.
RESULTS
A total of 189 DEPs was identified in the dataset, from which five DEPs related to sperm function and fertilization were selected for validation by Western blot. We were able to validate the underexpression of the mitochondrial complex subunits NADH:Ubiquinone Oxidoreductase Core Subunit S1 (NDUFS1) and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2), as well as the underexpression of the testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (ATP1A4) in the NSTC group.
CONCLUSIONS
Our results indicate that sperm mitochondrial dysfunction may explain the observed decrease in sperm concentration, total sperm count and total motile count in NSTC patients. The identified DEPs may serve as potential biomarkers for the pathophysiology of subfertility/infertility in patients with NSTC. Our study also associates the reduced fertilizing ability of NSTC patients with the dysregulation of important sperm molecular mechanisms.

Keyword

Cancer therapy; Male fertility; Non-seminoma; Sperm quality; Testicular cancer

MeSH Terms

Adenosine Triphosphatases
Biomarkers
Blotting, Western
Computational Biology
Cryopreservation
Dataset
Electron Transport Complex III
Fertility*
Fertilization
Humans
Male
Mass Spectrometry
Proteome
Semen
Sperm Count
Sperm Motility
Spermatozoa
Testicular Neoplasms*
Adenosine Triphosphatases
Biomarkers
Electron Transport Complex III
Proteome
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