Free circulating DNA and DNase activity in the ejaculates of men with spinal cord injury

Bartolomé-Nebreda, Javier; Vargas-Baquero, Eduardo; López‐Fernández, Carmen; Fernández, José Luis Fernández; Johnston, Stephen D.; Gosálvez, Jaime

doi:10.1038/s41393-020-0518-3

Cited by 5 publications

(6 citation statements)

References 29 publications

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“…Activated DNases during the apoptotic process results in highly degraded DNA explaining, in part, the presence of DSBs. This phenomenon would also help to explain the extreme presence of free circulating DNA (cfDNA) recently described in sperm from SCI patients, where a persistent cfDNA band of ∼150 bp was observed in the seminal plasma, occasionally accompanied by an additional band of ∼90 bp 7 …”

Section: Discussionmentioning

confidence: 78%

“…This phenomenon would also help to explain the extreme presence of free circulating DNA (cfDNA) recently described in sperm from SCI patients, where a persistent cfDNA band of ∼150 bp was observed in the seminal plasma, occasionally accompanied by an additional band of ∼90 bp 7. Following our summary of the possible mechanisms of SDF in sperm in men with SCI, it must be acknowledged that only restriction endonucleases from bacteria and type 2 topoisomerases can produce DSBs without accompanying SSBs.…”

mentioning

confidence: 62%

“…In SCI men, the origin of this damaged sperm DNA is most likely multifactorial, and has been related with irregular seminal vesicular secretions, abnormal seminal plasma chemistry, hormonal dysfunction, scrotal hyperthermia, anejaculation, as well as recurrent incidence of leukocytospermia and episodes of high levels of oxidative stress 5,6 . Further to these adverse scenarios for DNA stability, a high level of DNase activity has recently been reported in the seminal plasma of men with SCI, a phenomenon that is likely related to the high concentration of low molecular weight free‐circulating DNA in their seminal plasma 7 …”

Section: Introductionmentioning

confidence: 99%

“…5,6 Further to these adverse scenarios for DNA stability, a high level of DNase activity has recently been reported in the seminal plasma of men with SCI, a phenomenon that is likely related to the high concentration of low molecular weight free-circulating DNA in their seminal plasma. 7 Men with SCI are particularly affected by the incidence of high levels of oxidative stress, which is likely to be linked to the presence of elevated levels of active leukocytes. 4 In particular, oxidative stress produced from the presence of leukocytes, may induce SSBs with the formation of 8-oxo-7,8-dihydroguanine (8-oxo-dG) adducts from the original guanine on the DNA molecule.…”

Section: Introductionmentioning

confidence: 99%

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Sperm DNA damage in men with spinal cord injury: the relative incidence of single‐ and double‐strand DNA breaks

et al. 2022

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Background: Men with spinal cord injury (SCI) show a high proportion of sperm DNA damage in their ejaculate but the underlying pathology remains elusive.Objective: To investigate the relative incidence of single (SSBs) and double-strand DNA breaks (DSBs) and DNase activity in men with SCI. Materials and methods:This study included ejaculates of 20 men with SCI and 27 normozoospermic (sperm donors). A TwoTails comet assay (TTComet) allowed visualization of three categories of sperm DNA damage corresponding to SSBs, DSBs and those with a combination of SSBs and DSBs, facilitating accurate calculation of the total proportion of SSBs and DSBs. A subset of 15 individuals (sperm donors and SCI patients) was used to test for DNase activity in the seminal plasma.Results: While the proportion of DSBs in men with SCI (median-57.5%) was higher (P = 0.000) than normozoospermic samples (median-4.6%), the proportion of SSBs was higher (P = 0.022) in the normozoospermic ejaculates (median-6.0%) compared to men with SCI (median-2.5%). The relative proportion of the total DSBs with respect to the total SSBs was 3.3× in men with SCI but 0.9× in normozoospermic samples.We further confirmed the high DNase activity in the seminal plasma of men with SCI. Discussion: The TTComet assay provided new insights to the pathology of sperm DNA in men with SCI and may have diagnostic value in developing sperm selection methodologies to reduce DSBs prior to ART. Conclusion: Men with SCI are characterized by a high proportion of sperm with DSBs and high levels of DNase activity in the seminal plasma compared to normozoospermic men.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sperm DNA damage in men with spinal cord injury: the relative incidence of single‐ and double‐strand DNA breaks

et al. 2022

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“…On the other hand, we recently reported the massive presence of DNase activity in patients with spinal cord injury (SCI), while the ejaculates of these patients also possess extremely high levels of sperm with DNA damage. While this was an interesting observation, it is difficult to attribute a causal relationship to this correlation because of other contributing and potentially confounding factors that might cause SDF in these individuals [ 50 , 51 ]. Interestingly, we also described the presence of cell-free DNA (cf-DNA), represented by two main DNA electrophoresis bands of 90 and 150 bp, in the majority of these same patients ([ 51 ]; [ Figure 2 b]).…”

Section: Presence Of Dnase Activity In the Ejaculatementioning

confidence: 99%

Role of DNase Activity in Human Sperm DNA Fragmentation

Gosálvez,

Fernández,

Johnston

et al. 2024

Biomolecules

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In this clinical era of intracytoplasmic sperm injection (ICSI), where a single spermatozoon is chosen for fertilization, the diagnostic functionality of the classical parameters typically associated with fertilization, such as sperm concentration, sperm motility, acrosome integrity, and mitochondria, is perhaps becoming less critical. In contrast, the contribution of sperm DNA quality to our understanding of the impact of male fertility within the context of ICSI is gaining increasing interest and importance. Even with respect to natural conception, high levels of sperm DNA fragmentation (SDF) in the ejaculate can adversely affect reproductive outcomes. However, the precise origin of SDF pathology in sperm cells is often ambiguous and most likely to be multifactorial. Hence, the genetic makeup of an individual, unbalanced REDOX processes, enzymatic activity, environmental and lifestyle factors, and even damage during sperm handling in the laboratory all operate in a unique and often synergistic manner to produce or induce sperm DNA damage. Surprisingly, the contribution of active enzymes as potential agents of SDF has received much less attention and, therefore, is likely to be underrated. This review highlights the roles of different enzymes related to the degradation of sperm DNA as possible effectors of DNA molecules in spermatozoa.

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