{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T13:32:35Z","timestamp":1782567155276,"version":"3.54.5"},"reference-count":90,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,7]],"date-time":"2024-09-07T00:00:00Z","timestamp":1725667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Sperm DNA fragmentation (sDF) is a DNA damage able to predict natural conception. Thus, many laboratories added tests for the detection of sDF as an adjunct to routine semen analysis with specific indications. However, some points related to sDF are still open. The available tests are very different each from other, and a direct comparison, in terms of the prediction of reproductive outcomes, is mandatory. The proposed mechanisms responsible for sDF generation have not yielded treatments for men with high levels of sDF that have gained the general consent in clinical practice, thus requiring further research. Another relevant point is the biological meaning to attribute to sDF and, thus, what we can expect from tests detecting sDF for the diagnosis of male infertility. SDF can represent the \u201ctip of iceberg\u201d of a more extended and undetected sperm abnormality somehow impacting upon reproduction. Investigating the nature of such a sperm abnormality might provide novel insights into the link between sDF and reproduction. Finally, several studies reported an impact of native sDF on assisted reproduction technique outcomes. However, to fertilise the oocyte, selected spermatozoa are used where sDF, if present, associates with highly motile spermatozoa, which is the opposite situation to native semen, where most sDF associates with non-viable spermatozoa. Studies comparing the impact of sDF, as assessed in both native and selected spermatozoa, are needed.<\/jats:p>","DOI":"10.3390\/jcm13175309","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T05:06:06Z","timestamp":1725858366000},"page":"5309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sperm DNA Fragmentation in Male Infertility: Tests, Mechanisms, Meaning and Sperm Population to Be Tested"],"prefix":"10.3390","volume":"13","author":[{"given":"Donata","family":"Conti","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costanza","family":"Calamai","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Muratori","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,7]]},"reference":[{"key":"ref_1","first-page":"249","article-title":"WHO Fact Sheet on Infertility Gives Hope to Millions of Infertile Couples Worldwide","volume":"12","author":"Ombelet","year":"2020","journal-title":"Facts Views Vison Obgyn"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S2213-8587(16)30040-7","article-title":"Novel Concepts in the Aetiology of Male Reproductive Impairment","volume":"5","author":"Tournaye","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/biolre\/iox104","article-title":"Reactive Oxygen Species and Protein Modifications in Spermatozoa","volume":"97","year":"2017","journal-title":"Biol. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"James, E.R., Carrell, D.T., Aston, K.I., Jenkins, T.G., Yeste, M., and Salas-Huetos, A. (2020). The Role of the Epididymis and the Contribution of Epididymosomes to Mammalian Reproduction. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155377"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1056\/NEJMoa003005","article-title":"Sperm Morphology, Motility, and Concentration in Fertile and Infertile Men","volume":"345","author":"Guzick","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1093\/humrep\/deu082","article-title":"Semen Analysis and Prediction of Natural Conception","volume":"29","author":"Leushuis","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s40471-017-0098-8","article-title":"Fathers Matter: Why It\u2019s Time to Consider the Impact of Paternal Environmental Exposures on Children\u2019s Health","volume":"4","author":"Braun","year":"2017","journal-title":"Curr. Epidemiol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1093\/humupd\/dmv042","article-title":"Sperm Selection in Natural Conception: What Can We Learn from Mother Nature to Improve Assisted Reproduction Outcomes?","volume":"21","author":"Sakkas","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.fertnstert.2015.06.005","article-title":"DNA Fragmentation in Brighter Sperm Predicts Male Fertility Independently from Age and Semen Parameters","volume":"104","author":"Muratori","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e221","DOI":"10.1111\/j.1365-2605.2009.00995.x","article-title":"Sperm Chromatin Structure Assay as an Independent Predictor of Fertility in Vivo: A Case-Control Study","volume":"33","author":"Giwercman","year":"2010","journal-title":"Int. J. Androl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1093\/humrep\/dei231","article-title":"Sperm DNA Fragmentation: Threshold Value in Male Fertility","volume":"20","author":"Sergerie","year":"2005","journal-title":"Human. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.rbmo.2018.06.023","article-title":"Sperm DNA Fragmentation Index as a Promising Predictive Tool for Male Infertility Diagnosis and Treatment Management\u2014Meta-Analyses","volume":"37","author":"Santi","year":"2018","journal-title":"Reprod. Biomed. Online"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/j.2047-2927.2013.00111.x","article-title":"Comprehensive Analysis of Sperm DNA Fragmentation by Five Different Assays: TUNEL Assay, SCSA, SCD Test and Alkaline and Neutral Comet Assay","volume":"1","author":"Abad","year":"2013","journal-title":"Andrology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/humrep\/14.4.1039","article-title":"Utility of the Sperm Chromatin Structure Assay as a Diagnostic and Prognostic Tool in the Human Fertility Clinic","volume":"14","author":"Evenson","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.aju.2017.11.002","article-title":"Role of Sperm DNA Fragmentation in Male Factor Infertility: A Systematic Review","volume":"16","author":"Cho","year":"2018","journal-title":"Arab. J. Urol."},{"key":"ref_16","unstructured":"World Health Organization (2021). WHO Laboratory Manual for the Examination and Processing of Human Semen, World Health Organization."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.euf.2020.12.017","article-title":"European Association of Urology Guidelines Panel on Male Sexual and Reproductive Health: A Clinical Consultation Guide on the Indications for Performing Sperm DNA Fragmentation Testing in Men with Infertility and Testicular Sperm Extraction in Nonazoospermic Men","volume":"8","author":"Tharakan","year":"2022","journal-title":"Eur. Urol. Focus."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"412","DOI":"10.5534\/wjmh.200128","article-title":"Sperm DNA Fragmentation: A New Guideline for Clinicians","volume":"38","author":"Agarwal","year":"2020","journal-title":"World J. Mens. Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.theriogenology.2005.09.011","article-title":"Clinical Aspects of Sperm DNA Fragmentation Detection and Male Infertility","volume":"65","author":"Evenson","year":"2006","journal-title":"Theriogenology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e508","DOI":"10.1002\/cpz1.508","article-title":"Sperm Chromatin Structure Assay (SCSA\u00ae) for Fertility Assessment","volume":"2","author":"Evenson","year":"2022","journal-title":"Curr. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1006\/excr.1997.3719","article-title":"Susceptibility of Human Sperm to in Situ DNA Denaturation Is Strongly Correlated with DNA Strand Breaks Identified by Single-Cell Electrophoresis","volume":"236","author":"Aravindan","year":"1997","journal-title":"Exp. Cell Res."},{"key":"ref_22","first-page":"1011","article-title":"Human Sperm DNA Fragmentation: Correlation of TUNEL Results as Assessed by Flow Cytometry and Optical Microscopy","volume":"71","author":"Camejo","year":"2007","journal-title":"Cytom. A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/humrep\/den058","article-title":"Nuclear Staining Identifies Two Populations of Human Sperm with Different DNA Fragmentation Extent and Relationship with Semen Parameters","volume":"23","author":"Muratori","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1093\/humrep\/des348","article-title":"Semen Apoptotic M540 Body Levels Correlate with Testis Abnormalities: A Study in a Cohort of Infertile Subjects","volume":"27","author":"Lotti","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2605.2009.01042.x","article-title":"The TUNEL Assay Consistently Underestimates DNA Damage in Human Spermatozoa and Is Influenced by DNA Compaction and Cell Vitality: Development of an Improved Methodology","volume":"34","author":"Mitchell","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ribeiro, S.C., Muratori, M., De Geyter, M., and De Geyter, C. (2017). TUNEL Labeling with BrdUTP\/Anti-BrdUTP Greatly Underestimates the Level of Sperm DNA Fragmentation in Semen Evaluation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181802"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/978-1-62703-038-0_13","article-title":"Sperm DNA Damage Measured by Comet Assay","volume":"927","author":"Simon","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.5653\/cerm.2019.46.1.14","article-title":"Evaluation of Sperm DNA Fragmentation Using Multiple Methods: A Comparison of Their Predictive Power for Male Infertility","volume":"46","author":"Javed","year":"2019","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1093\/humrep\/deu040","article-title":"Comparative Analysis of Three Sperm DNA Damage Assays and Sperm Nuclear Protein Content in Couples Undergoing Assisted Reproduction Treatment","volume":"29","author":"Simon","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/j.1939-4640.2003.tb02641.x","article-title":"The Sperm Chromatin Dispersion Test: A Simple Method for the Determination of Sperm DNA Fragmentation","volume":"24","author":"Muriel","year":"2003","journal-title":"J. Androl."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cissen, M., van Wely, M., Scholten, I., Mansell, S., de Bruin, J.P., Mol, B.W., Braat, D., Repping, S., and Hamer, G. (2016). Measuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165125"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4103\/1008-682X.182822","article-title":"A Systematic Review and Meta-Analysis to Determine the Effect of Sperm DNA Damage on in Vitro Fertilization and Intracytoplasmic Sperm Injection Outcome","volume":"19","author":"Simon","year":"2017","journal-title":"Asian J. Androl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1111\/brv.12700","article-title":"Clinical Implications of Sperm DNA Damage in IVF and ICSI: Updated Systematic Review and Meta-Analysis","volume":"96","author":"Yeste","year":"2021","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1111\/1471-0528.17796","article-title":"Quantifying the Association of Sperm DNA Fragmentation with Assisted Reproductive Technology Outcomes: An Umbrella Review","volume":"131","author":"Maghraby","year":"2024","journal-title":"BJOG"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/BF00292448","article-title":"Molecular Mechanisms Involved in the Production of Chromosomal Aberrations. III. Restriction Endonucleases","volume":"90","author":"Natarajan","year":"1984","journal-title":"Chromosoma"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ribas-Maynou, J., Garc\u00eda-Peir\u00f3, A., Fernandez-Encinas, A., Amengual, M.J., Prada, E., Cort\u00e9s, P., Navarro, J., and Benet, J. (2012). Double Stranded Sperm DNA Breaks, Measured by Comet Assay, Are Associated with Unexplained Recurrent Miscarriage in Couples without a Female Factor. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044679"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s10815-021-02129-w","article-title":"Sperm Selection during ICSI Treatments Reduces Single- but Not Double-Strand DNA Break Values Compared to the Semen Sample","volume":"38","author":"Benet","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/andr.12324","article-title":"An Investigation of the Potential Effect of Sperm Nuclear Vacuoles in Human Spermatozoa on DNA Fragmentation Using a Neutral and Alkaline Comet Assay","volume":"5","author":"Pastuszek","year":"2017","journal-title":"Andrology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1111\/andr.12819","article-title":"DNA Fragmentation of Human Spermatozoa: Simple Assessment of Single- and Double-Strand DNA Breaks and Their Respective Dynamic Behavioral Response","volume":"8","author":"Otero","year":"2020","journal-title":"Andrology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, T.-E., Lee, C.-I., Huang, C.-C., Tsao, H.-M., Chang, H.-C., Chang, L.-S., Chang, T.A., Lee, M.-S., and Hsu, C.-T. (2023). Innovative Technology for Evaluation of Sperm DNA Double-Strand Breaks Diagnoses Male Factor Infertility and Prevents Reproductive Failures. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-46049-4"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Szab\u00f3, A., V\u00e1ncsa, S., Hegyi, P., V\u00e1radi, A., Forintos, A., Filipov, T., \u00c1cs, J., \u00c1cs, N., Szarvas, T., and Nyir\u00e1dy, P. (2023). Lifestyle-, Environmental-, and Additional Health Factors Associated with an Increased Sperm DNA Fragmentation: A Systematic Review and Meta-Analysis. Reprod. Biol. Endocrinol., 21.","DOI":"10.1186\/s12958-023-01054-0"},{"key":"ref_42","first-page":"2725","article-title":"Luminal Fluid of Epididymis and Vas Deferens Contributes to Sperm Chromatin Fragmentation","volume":"30","author":"Gawecka","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1093\/humrep\/15.4.830","article-title":"Study of Apoptotic DNA Fragmentation in Human Spermatozoa","volume":"15","author":"Gandini","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1007\/s10815-019-01579-7","article-title":"Novel Association between Apoptotic Sperm Biomarkers with Seminal Biochemical Parameters and Acetylcholinesterase Activity in Patients with Teratozoospermia","volume":"36","author":"Ammar","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3109\/19396368.2013.821540","article-title":"The Relationship between Seminal Leukocytes, Oxidative Status in the Ejaculate, and Apoptotic Markers in Human Spermatozoa","volume":"59","author":"Mupfiga","year":"2013","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Asadi, A., Ghahremani, R., Sc, M., Abdolmaleki, A., Rajaei, F., and Abbas, A. (2021). Role of Sperm Apoptosis and Oxidative Stress in Male Infertility: A Narrative Review. Int. J. Reprod. BioMedicine, 19.","DOI":"10.18502\/ijrm.v19i6.9371"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00418-020-01900-x","article-title":"Global Changes in Epigenomes during Mouse Spermatogenesis: Possible Relation to Germ Cell Apoptosis","volume":"154","author":"Koji","year":"2020","journal-title":"Histochem. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1095\/biolreprod61.6.1541","article-title":"Apoptosis Is Physiologically Restricted to a Specialized Cytoplasmic Compartment in Rat Spermatids","volume":"61","year":"1999","journal-title":"Biol. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1095\/biolreprod.107.064162","article-title":"DNA Damage Response during Chromatin Remodeling in Elongating Spermatids of Mice","volume":"78","author":"Leduc","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2119\/molmed.2014.00158","article-title":"Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress","volume":"21","author":"Muratori","year":"2015","journal-title":"Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.21037\/tau-23-415","article-title":"Outcomes Comparison of Testicular versus Ejaculated Sperm for Intracytoplasmic Sperm Injection in Infertile Men with High DNA Fragmentation: Updated Systematic Review and Meta-Analysis","volume":"12","author":"Zhao","year":"2023","journal-title":"Transl. Androl. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Len, J.S., Koh, W.S.D., and Tan, S.-X. (2019). The Roles of Reactive Oxygen Species and Antioxidants in Cryopreservation. Biosci. Rep., 39.","DOI":"10.1042\/BSR20191601"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1093\/humrep\/deu204","article-title":"Potential Importance of Transition Metals in the Induction of DNA Damage by Sperm Preparation Media","volume":"29","author":"Aitken","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.reprotox.2021.10.004","article-title":"Novel Methods to Detect ROS in Viable Spermatozoa of Native Semen Samples","volume":"106","author":"Riley","year":"2021","journal-title":"Reprod. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1071\/RD15325","article-title":"Causes and Consequences of Oxidative Stress in Spermatozoa","volume":"28","author":"Aitken","year":"2016","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1111\/andr.13375","article-title":"DNA Damage in Testicular Germ Cells and Spermatozoa. When and How Is It Induced? How Should We Measure It? What Does It Mean?","volume":"11","author":"Aitken","year":"2023","journal-title":"Andrology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1093\/humrep\/deq214","article-title":"Analysis of the Relationships between Oxidative Stress, DNA Damage and Sperm Vitality in a Patient Population: Development of Diagnostic Criteria","volume":"25","author":"Aitken","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Muratori, M., Pellegrino, G., Mangone, G., Azzari, C., Lotti, F., Tarozzi, N., Boni, L., Borini, A., Maggi, M., and Baldi, E. (2020). DNA Fragmentation in Viable and Non-Viable Spermatozoa Discriminates Fertile and Subfertile Subjects with Similar Accuracy. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051341"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Punjabi, U., Goovaerts, I., Peeters, K., and De Neubourg, D. (2023). Antioxidants in Male Infertility-If We Want to Get This Right We Need to Take the Bull by the Horns: A Pilot Study. Antioxidants, 12.","DOI":"10.3390\/antiox12101805"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.reprotox.2022.08.006","article-title":"Juvenile Exposure and Adult Risk Assessment with Single versus Repeated Exposure of Melphalan in the Germ Cells of Male SD Rat: Deciphering the Molecular Mechanisms","volume":"113","author":"Panghal","year":"2022","journal-title":"Reprod. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1002\/tox.23611","article-title":"Polystyrene Microplastics Induce Apoptosis and Necroptosis in Swine Testis Cells via ROS\/MAPK\/HIF1\u03b1 Pathway","volume":"37","author":"Wang","year":"2022","journal-title":"Environ. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1677\/JOE-07-0637","article-title":"Pathways Involved in Testicular Germ Cell Apoptosis in Immature Rats after FSH Suppression","volume":"197","author":"Ruwanpura","year":"2008","journal-title":"J. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1093\/humrep\/17.7.1811","article-title":"In-Vitro Effects of FSH and Testosterone Withdrawal on Caspase Activation and DNA Fragmentation in Different Cell Types of Human Seminiferous Epithelium","volume":"17","author":"Tesarik","year":"2002","journal-title":"Human Reprod."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1095\/biolreprod62.5.1146","article-title":"Qualitative and Quantitative Decline in Spermatogenesis of the Follicle-Stimulating Hormone Receptor Knockout (FORKO) Mouse","volume":"62","author":"Krishnamurthy","year":"2000","journal-title":"Biol. Reprod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/andr.12333","article-title":"Short-term FSH Treatment and Sperm Maturation: A Prospective Study in Idiopathic Infertile Men","volume":"5","author":"Casamonti","year":"2017","journal-title":"Andrology"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lispi, M., Drakopoulos, P., Spaggiari, G., Caprio, F., Colacurci, N., Simoni, M., and Santi, D. (2022). Testosterone Serum Levels Are Related to Sperm DNA Fragmentation Index Reduction after FSH Administration in Males with Idiopathic Infertility. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102599"},{"key":"ref_67","first-page":"e42583","article-title":"The Impact of Oxidative Stress on Male Reproductive Function: Exploring the Role of Antioxidant Supplementation","volume":"15","author":"Walke","year":"2023","journal-title":"Cureus"},{"key":"ref_68","first-page":"e54253","article-title":"Impact of Antioxidants on Conventional and Advanced Sperm Function Parameters: An Updated Review","volume":"16","author":"Alharbi","year":"2024","journal-title":"Cureus"},{"key":"ref_69","first-page":"CD007411","article-title":"Antioxidants for Male Subfertility","volume":"3","author":"Smits","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_70","first-page":"CD007411","article-title":"Antioxidants for Male Subfertility","volume":"5","author":"Smits","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/andr.12724","article-title":"An Update on Clinical and Surgical Interventions to Reduce Sperm DNA Fragmentation in Infertile Men","volume":"8","author":"Esteves","year":"2020","journal-title":"Andrology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.fertnstert.2017.06.018","article-title":"Reproductive Outcomes of Testicular versus Ejaculated Sperm for Intracytoplasmic Sperm Injection among Men with High Levels of DNA Fragmentation in Semen: Systematic Review and Meta-Analysis","volume":"108","author":"Esteves","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.euf.2023.08.008","article-title":"Does Testicular Sperm Improve Intracytoplasmic Sperm Injection Outcomes for Nonazoospermic Infertile Men with Elevated Sperm DNA Fragmentation? A Systematic Review and Meta-Analysis","volume":"10","author":"Khoo","year":"2024","journal-title":"Eur. Urol. Focus."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.fertnstert.2020.10.045","article-title":"Oocyte Ability to Repair Sperm DNA Fragmentation: The Impact of Maternal Age on Intracytoplasmic Sperm Injection Outcomes","volume":"116","author":"Setti","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/humrep\/deh127","article-title":"Late, but Not Early, Paternal Effect on Human Embryo Development Is Related to Sperm DNA Fragmentation","volume":"19","author":"Tesarik","year":"2004","journal-title":"Human. Reprod."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ribas-Maynou, J., and Benet, J. (2019). Single and Double Strand Sperm DNA Damage: Different Reproductive Effects on Male Fertility. Genes, 10.","DOI":"10.3390\/genes10020105"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/j.1939-4640.2002.tb02599.x","article-title":"Sperm Chromatin Structure Assay: Its Clinical Use for Detecting Sperm DNA Fragmentation in Male Infertility and Comparisons with Other Techniques","volume":"23","author":"Evenson","year":"2002","journal-title":"J. Androl."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mrfmmm.2012.03.006","article-title":"DNA Fragmentation Dynamics Allows the Assessment of Cryptic Sperm Damage in Human: Evaluation of Exposure to Ionizing Radiation, Hyperthermia, Acidic PH and Nitric Oxide","volume":"734","author":"Santiso","year":"2012","journal-title":"Mutat. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.fertnstert.2010.06.053","article-title":"Protamine 1 to Protamine 2 Ratio Correlates with Dynamic Aspects of DNA Fragmentation in Human Sperm","volume":"95","author":"Abad","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.fertnstert.2008.08.136","article-title":"A Dynamic Assessment of Sperm DNA Fragmentation versus Sperm Viability in Proven Fertile Human Donors","volume":"92","author":"Caballero","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.fertnstert.2008.05.068","article-title":"Sperm Deoxyribonucleic Acid Fragmentation Dynamics in Fertile Donors","volume":"92","author":"Caballero","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Muratori, M., Tarozzi, N., Carpentiero, F., Danti, S., Perrone, F.M., Cambi, M., Casini, A., Azzari, C., Boni, L., and Maggi, M. (2019). Sperm Selection with Density Gradient Centrifugation and Swim up: Effect on DNA Fragmentation in Viable Spermatozoa. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-43981-2"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e3624","DOI":"10.1097\/MD.0000000000003624","article-title":"Variation of DNA Fragmentation Levels During Density Gradient Sperm Selection for Assisted Reproduction Techniques: A Possible New Male Predictive Parameter of Pregnancy?","volume":"95","author":"Muratori","year":"2016","journal-title":"Medicine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1074\/mcp.RA119.001626","article-title":"Proteomic Analysis Reveals That Topoisomerase 2A Is Associated with Defective Sperm Head Morphology","volume":"19","author":"Netherton","year":"2020","journal-title":"Mol. Cell Proteom."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"S734","DOI":"10.21037\/tau.2017.08.20","article-title":"A Strengths-Weaknesses-Opportunities-Threats (SWOT) Analysis on the Clinical Utility of Sperm DNA Fragmentation Testing in Specific Male Infertility Scenarios","volume":"6","author":"Esteves","year":"2017","journal-title":"Transl. Androl. Urol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/humrep\/dem353","article-title":"Sperm Chromatin Structure Assay Parameters Measured after Density Gradient Centrifugation Are Not Predictive for the Outcome of ART","volume":"23","author":"Bungum","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.rbmo.2011.08.010","article-title":"Relationships between Human Sperm Protamines, DNA Damage and Assisted Reproduction Outcomes","volume":"23","author":"Simon","year":"2011","journal-title":"Reprod. Biomed. Online"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhang, X., Chao, S., Ye, N., and Ouyang, D. (2024). Emerging Trends in Sperm Selection: Enhancing Success Rates in Assisted Reproduction. Reprod. Biol. Endocrinol., 22.","DOI":"10.1186\/s12958-024-01239-1"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.fertnstert.2023.05.157","article-title":"Artificial Intelligence for Sperm Selection\u2014A Systematic Review","volume":"120","author":"Cherouveim","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/andr.13578","article-title":"Microfluidics: The Future of Sperm Selection in Assisted Reproduction","volume":"12","author":"Jahangiri","year":"2024","journal-title":"Andrology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/17\/5309\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:50:15Z","timestamp":1760111415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/17\/5309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,7]]},"references-count":90,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["jcm13175309"],"URL":"https:\/\/doi.org\/10.3390\/jcm13175309","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,7]]}}}