Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients.

Manesh Kumar Panner Selvam,Saradha Baskaran,Renata Finelli,Ashok Agarwal

doi:10.3390/ijms21186754

Manesh Kumar Panner Selvam, Saradha Baskaran + Show 2 more

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https://doi.org/10.3390/ijms21186754

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Abstract

Cancer has adverse effects on male reproductive health. Conventional semen analysis does not explain the molecular changes in the spermatozoa of cancer patients. Currently, proteomics is being widely used to identify the fertility-associated molecular pathways affected in spermatozoa. The objective of this study was to evaluate the sperm proteome of patients with various types of cancer. Cryopreserved semen samples from patients (testicular cancer, n = 40; Hodgkin’s disease, n = 32; lymphoma, n = 20; leukemia, n = 17) before starting therapy were used for proteomic analysis, while samples from fertile donors (n = 19) were included as controls. The proteomic profiling of sperm was carried out by liquid chromatography-tandem mass spectrometry, and differentially expressed proteins involved in the reproductive processes were validated by Western blotting. Bioinformatic analysis revealed that proteins associated with mitochondrial dysfunction, oxidative phosphorylation, and Sirtuin signaling pathways were dysregulated in cancer patients, while oxidative phosphorylation and tricarboxylic acid cycle were predicted to be deactivated. Furthermore, the analysis revealed dysregulation of key proteins associated with sperm fertility potential and motility (NADH:Ubiquinone oxidoreductase core subunit S1, superoxide dismutase 1, SERPINA5, and cytochrome b-c1 complex subunit 2) in the cancer group, which were further validated by Western blot. Dysfunctional molecular mechanisms essential for fertility in cancer patients prior to therapy highlight the potential impact of cancer phenotype on male fertility.

Highlights

Cancer in reproductive age can significantly affect fertility in males, representing one of the most common causes of infertility
The average values were within the physiological limits provided by the WHO guidelines, a significant reduction of sperm concentration was observed in all cancer groups, while a significant decline in sperm motility was noted in patients with testicular cancer and lymphoma when compared to the fertile donors
The analysis revealed the unde*reAxcptirveastsioionnoroifnaNctDivUatFioSn1 oafnpdathUwQaCysRaCre2 inindicaalltetdhbeycZansccoerre.tyApZessccoorme >p2arienddictaotetshaectfievrattiiloen men (Figuwrehi6leAa,Bv)a.luSeE

Summary

Introduction

Cancer in reproductive age can significantly affect fertility in males, representing one of the most common causes of infertility. The majority of people affected by cancer are >55 years old (~80%). In 2020, a high number of people in reproductive age (15–39 years old) are predicted to be affected by testicular cancer (6500 estimated new cases), Hodgkin’s lymphoma (2800 estimated new cases) and non-Hodgkin’s lymphoma (4600 estimated new cases), as well as leukemia (600 estimated new cases) in the United States [1]. As reported by the American Cancer Society, an increase in relative survival rate has been reported for all types of cancers since the 1960s. This may be due to early diagnosis and the availability of more effective treatments [1]. The possibility of achieving a future pregnancy is a concern for cancer patients [2]

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