{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:09:25Z","timestamp":1788793765718,"version":"build-2803163510"},"reference-count":21,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Cell-free DNA (cfDNA) fragments represent emerging biomarkers of major interest in the assessment of male fertility and the management of couples undergoing assisted reproductive technology (ART). Easy to quantify and present in most biological fluids, seminal cfDNA could reflect apoptosis and necrosis occurring within the male reproductive system. In this study, we compared cfDNA concentrations, measured by means of qPCR targeting the RNase P gene, in the seminal plasma of men with severe sperm quality abnormalities, including very severe asthenozoospermia (n = 25), total azoospermia (n = 25), very severe oligozoospermia (n = 25), and very severe teratozoospermia (n = 25), with those of normozoospermic controls (n = 25). Mean cfDNA concentrations were particularly elevated in men with azoospermia (5.47 \u00b1 1.17 \u00b5g\/mL) and very severe teratozoospermia (3.25 \u00b1 1.21 \u00b5g\/mL), compared with controls (1.96 \u00b1 0.27 \u00b5g\/mL). After adjustment for multiple testing, only azoospermia and very severe teratozoospermia remained significantly associated with increased cfDNA levels (Holm\u2013Bonferroni adjusted p &lt; 0.003), whereas the other phenotypes did not maintain statistical significance. These results suggest that seminal cfDNA is markedly increased in the most severe forms of spermatogenic impairment, potentially reflecting enhanced germ cell apoptosis or testicular cell involvement. Despite some limitations, including the modest sample size and single-center design, our observations support the value of cfDNA as a promising non-invasive biomarker of sperm quality. Larger multicenter and longitudinal studies are needed to validate its clinical relevance and determine standardized reference thresholds for clinical application.<\/jats:p>","DOI":"10.3390\/cimb48090911","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of the Correlation Between Circulating Cell-Free DNA (CfDNA) Levels and Serious Abnormal Sperm Parameters"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7983-5136","authenticated-orcid":false,"given":"Oumar","family":"Konate","sequence":"first","affiliation":[{"name":"Laboratory of Health, Environment and Biotechnology, Pathophysiology, Molecular Genetics and Biotechnology Team at the Ain Chock Faculty of Sciences, Hassan II University of Casablanca, Casablanca 20360, Morocco"},{"name":"Medical Analysis Laboratory, Reproductive Biology, Labomac, Casablanca 20100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0742-8080","authenticated-orcid":false,"given":"Modou Mamoune","family":"Mbaye","sequence":"additional","affiliation":[{"name":"Medical Analysis Laboratory, Reproductive Biology, Labomac, Casablanca 20100, Morocco"},{"name":"Immunopathology-Immunotherapy-Immunomonitoring Laboratory, Faculty of Medicine, Mohammed VI University of Health and Sciences, Casablanca 82403, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bouchra","family":"El Khalfi","sequence":"additional","affiliation":[{"name":"Laboratory of Health, Environment and Biotechnology, Pathophysiology, Molecular Genetics and Biotechnology Team at the Ain Chock Faculty of Sciences, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bouchra","family":"Ghazi","sequence":"additional","affiliation":[{"name":"Immunopathology-Immunotherapy-Immunomonitoring Laboratory, Faculty of Medicine, Mohammed VI University of Health and Sciences, Casablanca 82403, Morocco"},{"name":"Mohamed VI Center for Research & Innovation (CM6RI), Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatiha","family":"Elmellouli","sequence":"additional","affiliation":[{"name":"Regional Laboratory for Analysis and Research Casablanca, National Office for Food Safety \u201cONSSA\u201d, Rabat 10050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasnae","family":"Zekhnini","sequence":"additional","affiliation":[{"name":"Regional Laboratory for Analysis and Research Casablanca, National Office for Food Safety \u201cONSSA\u201d, Rabat 10050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noureddine","family":"Louanjli","sequence":"additional","affiliation":[{"name":"Medical Analysis Laboratory, Reproductive Biology, Labomac, Casablanca 20100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelaziz","family":"Soukri","sequence":"additional","affiliation":[{"name":"Laboratory of Health, Environment and Biotechnology, Pathophysiology, Molecular Genetics and Biotechnology Team at the Ain Chock Faculty of Sciences, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","first-page":"461","article-title":"An update on sperm retrieval techniques for azoospermic men","volume":"18","author":"Esteves","year":"2021","journal-title":"Nat. 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