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Hum. Reprod. Advance Access originally published online on March 17, 2008
Human Reproduction 2008 23(5):1044-1052; doi:10.1093/humrep/den081
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Characterization of sperm chromatin quality in testicular cancer and Hodgkin's lymphoma patients prior to chemotherapy

C. O'Flaherty1, F. Vaisheva1, B.F. Hales1, P. Chan2,4 and B. Robaire1,3,4,5

1 Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada 2 Department of Urology, McGill University, Montréal, Québec, Canada 3 Department of Obstetrics and Gynecology, McGill University, Montréal, Québec, Canada 4 McGill University Health Centre, Montréal, Québec, Canada

5 Correspondence address. Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William Osler, Montréal, Québec, Canada H3G 1Y6. E-mail: bernard.robaire{at}mcgill.ca

BACKGROUND: Although the incidences of testicular cancer and Hodgkin's lymphoma have increased in young men over the past decade, combination chemotherapy has improved survival. As fertility is of importance to these patients, characterization of sperm chromatin structure is needed. We assessed sperm chromatin in testicular cancer and Hodgkin's lymphoma patients prior to chemotherapy, in comparison with control community and idiopathic infertile volunteers.

METHODS: DNA damage was assessed with the sperm chromatin structure assay (SCSA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and comet assays; reactive thiols (SH) and DNA compaction were determined with the monobromobimane (mBBr) and chromomycin A3 (CMA3) assays, respectively.

RESULTS: Both testicular cancer (37%) and Hodgkin's lymphoma (81%) patients had normospermic samples with increased DNA damage, compared with controls. Cancer patients also had higher reactive thiols and CMA3 staining, indicating low DNA compaction.

CONCLUSIONS: Sperm DNA integrity and compaction were affected in testicular cancer and Hodgkin's lymphoma patients prior to chemotherapy. Although SCSA, TUNEL and comet assays all detected DNA damage, the latter was optimal for use in cancer patients. A combination of the comet assay with tests that evaluate sperm DNA compaction, such as flow cytometry-based CMA3 and mBBr assays, is a reliable strategy to characterize sperm chromatin quality in cancer patients at the time of sperm banking.

Key words: DNA strand breaks/nuclear compaction/CMA3/SCSA/comet assay

Submitted on August 8, 2007; resubmitted on February 8, 2008; accepted on February 22, 2008.


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