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

The World Journal of Men′s Health 2020년 38권 4호 p.521 ~ 534
Martins Ana D., Agarwal Ashok, Baskaran Saradha, Pushparaj Peter Natesan, Ahmad Gulfam, Selvam Manesh Kumar Panner,
소속 상세정보
 ( Martins Ana D. ) - Cleveland Clinic American Center for Reproductive Medicine
 ( Agarwal Ashok ) - Cleveland Clinic American Center for Reproductive Medicine
 ( Baskaran Saradha ) - Cleveland Clinic American Center for Reproductive Medicine
 ( Pushparaj Peter Natesan ) - King Abdulaziz University Center of Excellence in Genomic Medicine Research
 ( Ahmad Gulfam ) - Sydney University School of Medical Sciences Division of Pathology
 ( Selvam Manesh Kumar Panner ) - Cleveland Clinic American Center for Reproductive Medicine

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.

키워드

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

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