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

O’Flaherty, Cristián; Vaisheva, Farida; Hales, Barbara F.; Chan, Peter; Robaire, Bernard

doi:10.1093/humrep/den081

Cited by 113 publications

(91 citation statements)

References 41 publications

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“…genetic or developmental abnormalities) or due to secondary or extrinsic factors causing testicular or posttesticular injury (e.g. gonadotoxins, hyperthermia, oxidants, endocrine abnormalities) [2][3][4][5][6][7][8][9][10]. Investigators have suggested that protamine deficiency (with aberrant chromatin remodeling), reactive oxygen species (ROS) and abortive apoptosis may cause sperm DNA damage [11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

Belloc¹,

Benkhalifa²,

Cohen-Bacrie³

et al. 2014

J Assist Reprod Genet

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Background Sperm DNA damage is common in infertile men and is associated with poor semen parameters but the impact of an isolated sperm abnormality on sperm DNA damage has not been studied. Objective To evaluate sperm DNA damage in a large cohort of infertile men with isolated sperm defects. Design, setting and participants Retrospective study of 1084 consecutive, non-azoospermic infertile men with an isolated sperm defect: isolated oligozoospermia (iOligo), isolated asthenozoospermia (iAstheno) or isolated teratozoospermia (iTerato). Outcome measurements and statistical analysis We examined and compared clinical parameters, conventional semen parameters and %sperm DNA fragmentation (%SDF, assessed by flow cytometry-based Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling assay) in the three groups of men. Results and limitations The mean (±SD) %SDF was significantly higher in the iAstheno compared to the iOligo and iTerato groups (25.0±14.0 vs. 19.2±11.6 and 20.7±12.1 %, respectively, P<0.0001). Similarly, the proportion of men with high %SDF (>30 %) was significantly higher in the iAstheno compared to the iOligo and iTerato groups (31 % vs. 18 % and 19 %, respectively, P<0.0001). In the group of 713 men with iAstheno, %SDF was positively correlated with paternal age (r=0.20, P<0.0001) and inversely correlated with %progressive motility (r=−0.18, P<0.0001). In the subset of 218 men with iTerato, %SDF was also positively correlated with paternal age (r=0.15, P=0.018) and inversely correlated with %progressive motility (r=−0.26, P=0.0001). Conclusions In this large cohort of infertile men with isolated sperm abnormalities, we have found that the sperm DNA fragmentation level is highest in the men with sperm motility defects and that 31 % of these men have high levels of sperm DNA fragmentation. The data indicate that poor motility is the sperm parameter abnormality most closely related to sperm DNA damage.

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Section: Introductionmentioning

confidence: 99%

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

Belloc¹,

Benkhalifa²,

Cohen-Bacrie³

et al. 2014

J Assist Reprod Genet

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“…However, it remains uncertain whether the presence of cancer itself could affect sperm DNA integrity in TGCT patients. In fact, although several recent studies reported the increase in sperm DNA damage before treatment in patients with TGCT in reference to fertile controls (Meseguer et al, 2008;O'Flaherty et al, 2008), other studies indicated that DNA fragmentation was not significantly increased in TGCT patients in comparison with the controls (Ribeiro et al, 2008;Smit et al, 2010). The discrepancy between these studies may have been caused by the low numbers of patients studied, or bias in patient and control selections (Smit et al, 2010).…”

Section: Discussionmentioning

confidence: 95%

The polymorphichMSH5C85T allele augments radiotherapy-induced spermatogenic impairment

et al. 2016

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SUMMARYThe hMSH5 C85T polymorphism (encoding hMSH5 P29S) is associated with male infertility and radiation-induced apoptotic response. To date, however, the potential association of hMSH5 C85T polymorphism with DNA damage accumulation in spermatozoa of cancer patients treated with radiotherapy is largely unknown. We investigated hMSH5 C85T allele and genotype frequencies, routine semen analysis and sperm DNA Fragmentation Index (DFI) in 113 testicular germ cell tumor (TGCT) patients before and after radiotherapy. The hMSH5 C85T allele is not associated with the occurrence of TGCT. However, in comparison with the CC genotype, TGCT patients with the CT + TT genotypes showed significantly altered sperm counts, sperm morphology and DFI after radiotherapy. Finally, the results of the DSB repair assay demonstrated that hMSH5 P29S could enhance radiotherapy-induced DNA damage by unleashing error-prone non-homologous end joining. Together, our studies indicate that the hMSH5 C85T variation could have an impact on the severity of radiotherapy-provoked long-term side effects through compromising the repair of radiationinduced DNA lesions.

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“…Indeed, apoptotic insults are known to cause SDF (Tamburrino et al 2012;Muratori et al 2015). However, as mentioned above, whether the occurrence of cancer is per se a factor favouring SDF is questioned, because variable results, depending on the type of tumour and on the method used to evaluate the parameter, have been reported (O'Flaherty et al 2008;Meseguer et al 2008;Ribeiro et al 2008;Ståhl et al 2009;McDowell et al 2013). As such, we cannot exclude the possibility that the high postcryopreservation levels of SDF in cancer patients (Edelstein et al 2008;Meseguer et al 2008; present study) reflect damage due to the continuous presence of an altered seminal plasma during the cryopreservation procedure (including the thawing procedure, which lasts several minutes).…”

Section: Discussionmentioning

confidence: 99%

“…However, whether cancer is per se associated with increased SDF remains contentious. For example, in the case of testicular cancer, high levels of SDF have been reported in some studies (O'Flaherty et al 2008;Meseguer et al 2008), but not in others (Ribeiro et al 2008;Ståhl et al 2009;Smit et al 2010). Similarly, elevated SDF levels have been found in samples from men with non-Hodgkin's lymphoma by some (Meseguer et al 2008;Smit et al 2010), but not by others (O'Flaherty et al 2008;McDowell et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…For example, in the case of testicular cancer, high levels of SDF have been reported in some studies (O'Flaherty et al 2008;Meseguer et al 2008), but not in others (Ribeiro et al 2008;Ståhl et al 2009;Smit et al 2010). Similarly, elevated SDF levels have been found in samples from men with non-Hodgkin's lymphoma by some (Meseguer et al 2008;Smit et al 2010), but not by others (O'Flaherty et al 2008;McDowell et al 2013). Whether there are different levels of SDF following the cryopreservation of spermatozoa from men with cancer than from men with non-cancer pathologies is even less clear, with only two studies (Edelstein et al 2008;Meseguer et al 2008) evaluating post-cryopreservation SDF levels in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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Sperm DNA fragmentation in cryopreserved samples from subjects with different cancers

Cambi

Marchiani

Manigrasso

et al. 2017

Reprod. Fertil. Dev.

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Abstract. Sperm cryopreservation is widely used by cancer patients undergoing chemo-or radiotherapy. Evidence suggests that IVF outcome with cryopreserved spermatozoa from cancer patients is less successful. To determine whether sperm DNA fragmentation (SDF) is involved in the lower fertilising ability of cryopreserved spermatozoa of cancer patients, SDF was evaluated in thawed spermatozoa from 78 men affected by different cancers and 53 men with noncancer pathologies. SDF was assessed by the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL), propidium iodide (PI), flow cytometry procedure, which allows determination of two different cell populations (PI brighter and PI dimmer ) and thus to determine the percentage of DNA fragmented sperm in both. PI dimmer spermatozoa are totally unviable, whereas PI brighter spermatozoa with SDF may be motile and morphologically normal, having higher biological relevance in the reproductive process. We found that the proportion of DNA fragmented PI brighter cells was significantly higher in thawed spermatozoa from cancer than non-cancer patients. Moreover, a positive correlation was found between the degree of DNA fragmentation and sperm motility in the PIbrighter population of spermatozoa from cancer patients that wasn't seen in non-cancer patients. The results of the present study suggest that higher SDF levels may contribute to the lower IVF success of cryopreserved spermatozoa from cancer patients and that evaluation of SDF could complement genetic counselling as part of the routine management of cancer patients who seek fertility preservation.Additional keywords: cancer patients, flow cytometry, propidium iodide, terminal deoxyribonucleotidyl transferasemediated dUTP-digoxigenin nick end-labelling (TUNEL).

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

Cited by 113 publications

References 41 publications

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

The polymorphichMSH5C85T allele augments radiotherapy-induced spermatogenic impairment

Sperm DNA fragmentation in cryopreserved samples from subjects with different cancers

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