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PMID: 30588784 Published · ppublish English Journal Article

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

The world journal of men's health ·Vol. 38 ·No. 2 ·2020-04-00 ·Pages 198-207

Dias TR, Agarwal A, Pushparaj PN, Ahmad G, Sharma R

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.

Keywords
Cancer therapy Male fertility Non-seminoma Sperm quality Testicular cancer
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Dias Tania R ORCID
American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA. | Universidade da Beira Interior, Covilhã, Portugal. | 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.
Agarwal Ashok ORCID
American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA. [email protected].
Pushparaj Peter N ORCID
Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, Jeddah, Saudi Arabia.
Ahmad Gulfam ORCID
Division of Pathology, School of Medical Sciences, Sydney University, Sydney, Australia.
Sharma Rakesh ORCID
American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.
Conflict of Interest

Authors have no potential conflicts of interest to disclose.

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Article Info
Journal
The world journal of men's health
Abbr.
World J Mens Health
ISSN
2287-4208
DOI
10.5534/wjmh.180099
Email
[email protected]
Published
2020-04-00
Epub
2018-00-21
Pages
198-207
Language
English
Region
Korea (South)
NLM ID
101596899
PMCID
PMC7076305
Grants
Cleveland Clinic · United States of America
Fundação para a Ciência e a Tecnologia · SFRH/BD/109284/2015 · Portugal
Fulbright Program · E0585639 · Portugal
Corrections
CommentIn
PMID: 30917083
CommentIn
PMID: 32022522
External Links
PubMed source DOI: 10.5534/wjmh.180099 PMC Full Text View journal details
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