Testicular cancer and sperm DNA damage: short‐ and long‐term effects of antineoplastic treatment

Abstract

SUMMARYThe aim of this study was to investigate sperm DNA damage induced by chemo-and radiotherapy in patients with testicular cancer to provide data on the extent and persistence of nuclear damage that might affect individual reproductive potential. We evaluated pre-and post-antineoplastic treatment sperm DNA integrity, expressed as DNA Fragmentation Index (DFI), in a large caseload of testicular cancer patients by sperm chromatin structure assay. The mean total DFI for all patients at T0 was 18.0 AE 12.5%. Sperm chromatin profile was markedly impaired at T3 (27.7 AE 17.4%) and T6 (23.2 AE 15.3%), improving considerably at T12 and T24 (14.0 AE 8.9% and 14.4 AE 10.3%). After chemotherapy, we found a marked increase in DFI at T3 and T6 and a significant reduction at T12 and T24 in comparison with the baseline. In contrast, DFI increased at T3 and T6 after radiotherapy but the subsequent reduction was far less marked, reaching baseline values at T12 and T24. Finally, post-treatment DNA damage was not age or histotype dependent, but was more marked in the advanced stage of cancer. In this study, we showed that the chromatin profile may be affected in the months immediately following the end of the treatment, improving after 12-24 months. Our results thus indicate that post-treatment DNA damage is influenced both by the type and intensity of the therapy and by the pathological and clinical stage of the disease.

The polymorphichMSH5C85T allele augments radiotherapy-induced spermatogenic impairment

“…Another important finding from our current study is the lack of recovery of radiotherapyinduced sperm DNA damage seen in patients with the hMSH5 C85T variant. It has been observed that sperm from infertile men often contain more DNA damage -a likely contributing factor for poor reproduction (Zini et al, 2001;Paoli et al, 2015). A potentially intriguing observation of our current study is the higher pretreatment sperm counts in the CT + TT group of TGCT patients.…”

Sperm DNA Fragmentation Index and Hyaluronan Binding Ability in Men from Infertile Couples and Men with Testicular Germ Cell Tumor

“…Another study of chromatin integrity in 21 infertile and 15 postorchiectomy TGCT patients who were to undergo chemotherapy found mean DFI values (assessed by SCSA) to be significantly higher in both the infertile (22%) and TGCT patients (15%) in comparison to healthy controls (8%) [28]. Paoli et al [29] report a mean DFI score of 18.0 ± 12.5% in a group of 131 postorchiectomy TGCT patients awaiting chemotherapy (assessed by SCSA). Similarly, Spermon et al [30] report the median percentage of damaged sperm cells (assessed by TUNEL) to be 21% in postorchiectomy TGCT patients awaiting chemotherapy.…”

Fertility managment in testicular cancer: the need to establish a standardized and evidence‐based patient‐centric pathway

“…Raised DNA fragmentation, as quantitated by the DNA fragmentation index (DFI), is associated with decreased conception rates and early pregnancy loss . Paoli et al found that after chemotherapy DFI increases significantly 3 months post chemotherapy. At this time point, men had a mean DFI of 28% after one to two cycles of BEP, and 33% after three to four cycles; however, DFI returns to baseline after 9 months and there is a significant decrease at 12 and 24 months.…”