ArticleMolecular medicine (Cambridge, Mass.)2015
Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress.
Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 6 of them syntheses that pooled it.
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Who cites it
120 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Impact of short abstinence versus testicular sperm on sperm DNA fragmentation: a systematic review and meta-analysis.Archives of gynecology and obstetrics · 2024Pooled it
- Putative adverse outcome pathways for silver nanoparticle toxicity on mammalian male reproductive system: a literature review.Particle and fibre toxicology · 2023Pooled it
- The effect of acupuncture on oxidative stress: A systematic review and meta-analysis of animal models.PloS one · 2022Pooled it
- Pharmacogenetics of FSH Action in the Male.Frontiers in endocrinology · 2019Pooled it
- The use of follicle stimulating hormone (FSH) for the treatment of the infertile man: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS).Journal of endocrinological investigation · 2018Guideline
- Does air pollution play a role in infertility?: a systematic review.Environmental health : a global access science source · 2017Pooled it
- Sperm DNA Fragmentation in Native Semen: A Reflection of Apoptotic and Non-Viable Spermatozoa and Its Implications for Assisted Reproduction.International journal of molecular sciences · 2026Article
- Sperm DNA fragmentation: how to test, when to test, and what to do with abnormal results-a pragmatic mini-review for clinical practice.Human reproduction (Oxford, England) · 2026Review
- Biological and clinical factors predicting sperm retrieval success in men with non-obstructive azoospermia.Reproduction & fertility · 2026Review
- Reactive Oxygen and Nitrogen Species in Male Reproductive Health: From Molecular Mechanisms to Clinical Consequences.Antioxidants (Basel, Switzerland) · 2026Review
- Oxidative Stress, Sperm DNA Fragmentation, or Both? Optimizing Test Selection in Male Infertility Evaluation.Antioxidants (Basel, Switzerland) · 2026Review
- Exploring the nexus between particulate matter and infertility: Multiple mechanistic insights and potential control strategies.iScience · 2026Review
- Comparing Methods for Sperm DNA Fragmentation Detection.Advances in experimental medicine and biology · 2026Review
- A comparison of sperm parameters DNA fragmentation and telomere length in testicular versus ejaculated spermatozoa.Scientific reports · 2025Article
- The role of sperm DNA fragmentation in reproduction: a SWOT analysis.Journal of assisted reproduction and genetics · 2025Review
- Diabetes and male infertility: A review of sperm chromatin damage and epigenetic effects.International journal of reproductive biomedicine · 2025Review
- Hurdles of Sperm Success: Exploring the Role of DNases.International journal of molecular sciences · 2025Review
- The Utility of Sperm DNA Fragmentation as a Diagnostic Tool for Male Infertility and Its Predictive Value for Assisted Reproductive Technology Outcomes.International journal of molecular sciences · 2025Article
- Fenofibrate ameliorated atorvastatin and piperine-induced ROS mediated reproductive toxicity in male Wistar rats.Toxicology reports · 2025Article
- Insulin‑like growth factor 2 in spermatogenesis dysfunction (Review).Molecular medicine reports · 2025Review
60 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sperm DNA fragmentation (sDF) represents a threat to male fertility, human reproduction and the health of the offspring. The causes of sDF are still unclear, even if apoptosis, oxidative assault and defects in chromatin maturation are hypothesized. Using multicolor flow cytometry and sperm sorting, we challenged the three hypothesized mechanisms by simultaneously evaluating sDF and signs of oxidative damage (8-hydroxy, 2'-deoxyguanosine [8-OHdG] and malondialdehyde [MDA]), apoptosis (caspase activity and cleaved poly[ADP-ribose] polymerase [cPARP]) and sperm immaturity (creatine phosphokinase [CK] and excess of residual histones). Active caspases and c-PARP were concomitant with sDF in a high percentage of spermatozoa (82.6% ± 9.1% and 53.5% ± 16.4%, respectively). Excess of residual histones was significantly higher in DNA-fragmented sperm versus sperm without DNA fragmentation (74.8% ± 17.5% and 37.3% ± 16.6%, respectively, p < 0.005), and largely concomitant with active caspases. Conversely, oxidative damage was scarcely concomitant with sDF in the total sperm population, at variance with live sperm, where 8-OHdG and MDA were clearly associated to sDF. In addition, most live cells with active caspase also showed 8-OHdG, suggesting activation of apoptotic pathways in oxidative-injured live cells. This is the first investigation on the origin of sDF directly evaluating the simultaneous presence of the signs of the hypothesized mechanisms with DNA breaks at the single cell level. The results indicate that the main pathway leading to sperm DNA breaks is a process of apoptosis, likely triggered by an impairment of chromatin maturation in the testis and by oxidative stress during the transit in the male genital tract. These findings are highly relevant for clinical studies on the effects of drugs on sDF and oxidative stress in infertile men and for the development of new therapeutic strategies.
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