Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients
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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/18/6754 |
| _version_ | 1797553700688887808 |
|---|---|
| author | Manesh Kumar Panner Selvam Renata Finelli Saradha Baskaran Ashok Agarwal |
| author_facet | Manesh Kumar Panner Selvam Renata Finelli Saradha Baskaran Ashok Agarwal |
| author_sort | Manesh Kumar Panner Selvam |
| collection | DOAJ |
| description | 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, <i>n</i> = 40; Hodgkin’s disease, <i>n</i> = 32; lymphoma, <i>n</i> = 20; leukemia, <i>n</i> = 17) before starting therapy were used for proteomic analysis, while samples from fertile donors (<i>n</i> = 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. |
| first_indexed | 2024-03-10T16:19:18Z |
| format | Article |
| id | doaj.art-2294ccaeeb0848dbbb4388bb931da1e5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:19:18Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2294ccaeeb0848dbbb4388bb931da1e52023-11-20T13:44:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118675410.3390/ijms21186754Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer PatientsManesh Kumar Panner Selvam0Renata Finelli1Saradha Baskaran2Ashok Agarwal3American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USAAmerican Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USAAmerican Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USAAmerican Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USACancer 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, <i>n</i> = 40; Hodgkin’s disease, <i>n</i> = 32; lymphoma, <i>n</i> = 20; leukemia, <i>n</i> = 17) before starting therapy were used for proteomic analysis, while samples from fertile donors (<i>n</i> = 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.https://www.mdpi.com/1422-0067/21/18/6754bioinformaticscancermale infertilityproteomicssperm |
| spellingShingle | Manesh Kumar Panner Selvam Renata Finelli Saradha Baskaran Ashok Agarwal Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients International Journal of Molecular Sciences bioinformatics cancer male infertility proteomics sperm |
| title | Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients |
| title_full | Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients |
| title_fullStr | Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients |
| title_full_unstemmed | Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients |
| title_short | Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients |
| title_sort | dysregulation of key proteins associated with sperm motility and fertility potential in cancer patients |
| topic | bioinformatics cancer male infertility proteomics sperm |
| url | https://www.mdpi.com/1422-0067/21/18/6754 |
| work_keys_str_mv | AT maneshkumarpannerselvam dysregulationofkeyproteinsassociatedwithspermmotilityandfertilitypotentialincancerpatients AT renatafinelli dysregulationofkeyproteinsassociatedwithspermmotilityandfertilitypotentialincancerpatients AT saradhabaskaran dysregulationofkeyproteinsassociatedwithspermmotilityandfertilitypotentialincancerpatients AT ashokagarwal dysregulationofkeyproteinsassociatedwithspermmotilityandfertilitypotentialincancerpatients |