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

Authors
  • Dias, Tania R1, 2, 3
  • Agarwal, Ashok4
  • Pushparaj, Peter N5
  • Ahmad, Gulfam6
  • Sharma, Rakesh1
  • 1 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.
  • 2 Universidade da Beira Interior, Covilhã, Portugal. , (Portugal)
  • 3 Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar and Unit for Multidisciplinary Research in Biomedicine, University of Porto, Porto, Portugal. , (Portugal)
  • 4 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA. [email protected]
  • 5 Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, Jeddah, Saudi Arabia. , (Saudi Arabia)
  • 6 Division of Pathology, School of Medical Sciences, Sydney University, Sydney, Australia. , (Australia)
Type
Published Article
Journal
The world journal of men's health
Publication Date
Apr 01, 2020
Volume
38
Issue
2
Pages
198–207
Identifiers
DOI: 10.5534/wjmh.180099
PMID: 30588784
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. 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. Copyright © 2020 Korean Society for Sexual Medicine and Andrology.

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