World J Mens Health.  2020 Oct;38(4):521-534. 10.5534/wjmh.190012.

Alterations of Spermatozoa Proteomic Profile in Men with Hodgkin’s Disease Prior to Cancer Therapy

Affiliations
  • 1American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.
  • 2Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar and Unit for Multidisciplinary Research in Biomedicine, University of Porto, Porto, Portugal
  • 3Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
  • 4Discipline of Pathology, School of Medical Sciences, Sydney University, Sydney, Australia.

Abstract

Purpose
Hodgkin’s disease (HD) is a type of cancer affecting men in the reproductive age with potential consequences on their fertility status. This study aims to analyze sperm parameters, alterations in proteomic profiles and validate selected protein biomarkers of spermatozoa in men with HD undergoing sperm banking before cancer therapy.
Materials and Methods
Semen analysis was carried out in healthy fertile donors (control, n=42), and patients diagnosed with HD (patients, n=38) before cancer therapy. We compared proteomic profiles of spermatozoa from donors (n=3) and patients (n=3) using LTQ-Orbitrap Elite hybrid MS system.
Results
A total of 1,169 proteins were identified by global proteomic in both groups. The ingenuity pathway analysis revealed that differentially expressed proteins involved in capacitation, acrosome reaction, binding of sperm to the zona pellucida, sperm motility, regulation of sperm DNA damage, and apoptosis were significantly downregulated in HD patients. Validation of proteins implicated in sperm fertility potential by Western Blot demonstrated that peroxiredoxin 2 (PRDX 2) was underexpressed (p=0.015), and transferrin (p=0.045) and SERPIN A5 (p=0.010) protein levels were overexpressed in spermatozoa of men with HD.
Conclusions
Findings of this study indicates that the key proteins involved in sperm fertility potential are significantly altered in men with HD, which provides substantial explanation for the observed low sperm quality in HD subjects prior to cancer therapy. Furthermore, our results suggest PRDX 2, transferrin and SERPIN A5 as possible candidate proteins for assessing sperm quality in HD patients prior to cancer therapy.

Keyword

Hodgkin disease; Infertility; Mass spectrometry; Proteomics; Spermatozoa; Transferrin
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