{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:28:34Z","timestamp":1786969714401,"version":"build-2736575974"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Sperm cryopreservation is widely used for male fertility preservation and assisted reproduction technologies; however, the freezing and thawing process can induce irreversible structural and functional damage to human spermatozoa. This review summarizes the main mechanisms through which cryopreservation disrupts redox homeostasis, with particular emphasis on the generation of reactive oxygen species, mitochondrial dysfunction, lipid peroxidation, DNA fragmentation, and the consequent impairment of sperm motility and viability. Human spermatozoa are particularly vulnerable to oxidative damage because they possess limited cytoplasmic antioxidant defenses and a plasma membrane rich in polyunsaturated fatty acids (PFA), which are highly susceptible to peroxidative injury. In addition, the dilution or removal of seminal plasma during cryopreservation further compromise extracellular antioxidant protection. Experimental studies have shown that supplementation of freezing and\/or thawing media with enzymatic and non-enzymatic antioxidants, including catalase, glutathione, ascorbic acid, tocopherols, melatonin, resveratrol, quercetin, MitoTEMPO, myo-inositol, elamipretide, brain-derived neurotrophic factor, and various natural extracts, may improve selected post-thaw sperm parameters and reduce biomarkers of oxidative stress. Nevertheless, no antioxidant strategy currently available is capable of completely preventing cryodamage, and the market heterogeneity of existing protocols limits their clinical translation. Further well-designed human studies are therefore required to determine the safety, efficacy, optimal concentration, and clinical utility of antioxidant supplementation in sperm cryopreservation media.<\/jats:p>","DOI":"10.3389\/fmed.2026.1870054","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:08:10Z","timestamp":1786968490000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Reactive oxygen species and antioxidant strategies in human sperm cryodamage"],"prefix":"10.3389","volume":"13","author":[{"given":"Luca","family":"Tramontano","sequence":"first","affiliation":[{"name":"R\u00e9seau Hospitalier Neuch\u00e2telois (RHNE)","place":["Neuch\u00e2tel, Switzerland"]},{"name":"H\u00f4pital de La Tour","place":["Meyrin, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Marci","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Ferrara","place":["Ferrara, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romualdo","family":"Sciorio","sequence":"additional","affiliation":[{"name":"Vitrolife Sweden AB","place":["V\u00e4stra Fr\u00f6lunda, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Wenger","sequence":"additional","affiliation":[{"name":"H\u00f4pital de La Tour","place":["Meyrin, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.bpobgyn.2018.12.004","article-title":"Fertility preservation in male patients with cancer","volume":"55","author":"Barak","year":"2019","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s10147-018-1333-0","article-title":"Preservation of fertility of adult male cancer patients treated with chemotherapy","volume":"24","author":"Kawai","year":"2019","journal-title":"Int J Clin Oncol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.bpobgyn.2018.07.007","article-title":"Setting up a fertility preservation programme","volume":"55","author":"Stern","year":"2019","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"854837","DOI":"10.1155\/2012\/854837","article-title":"Human sperm cryopreservation: update on techniques, effect on DNA integrity, and implications for ART","volume":"2012","author":"Di Santo","year":"2012","journal-title":"Adv Urol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.rbmo.2018.05.012","article-title":"Sperm cryopreservation: a review on current molecular cryobiology and advanced approaches","volume":"37","author":"Hezavehei","year":"2018","journal-title":"Reprod Biomed Online"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1016\/j.fertnstert.2013.08.005","article-title":"Semen cryopreservation for men banking for oligospermia, cancers, and other pathologies: prediction of post-thaw outcome using basal semen quality","volume":"100","author":"Degl'Innocenti","year":"2013","journal-title":"Fertil Steril"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1007\/s10561-016-9566-5","article-title":"The role of antioxidants in sperm freezing: a review","volume":"17","author":"Amidi","year":"2016","journal-title":"Cell Tissue Bank"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.fertnstert.2013.11.020","article-title":"Thawed human sperm quality is influenced by the volume of the cryopreserved specimen","volume":"101","author":"Abush","year":"2014","journal-title":"Fertil Steril"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1093\/humupd\/dmu063","article-title":"The effect of cryopreservation on the genome of gametes and embryos: principles of cryobiology and critical appraisal of the evidence","volume":"21","author":"Kopeika","year":"2015","journal-title":"Hum Reprod Update"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1016\/j.fertnstert.2016.09.004","article-title":"Supplementation of freezing and thawing media with brain-derived neurotrophic factor protects human sperm from freeze-thaw-induced damage","volume":"106","author":"Najafi","year":"2016","journal-title":"Fertil Steril"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/978-3-030-21664-1","article-title":"Cryopreservation of sperm: effects on chromatin and strategies to prevent them","volume":"1166","author":"Paoli","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1089\/bio.2019.0037","article-title":"Strategies to minimize various stress-related freeze-thaw damages during conventional cryopreservation of mammalian spermatozoa","volume":"17","author":"Kumar","year":"2019","journal-title":"Biopreserv Biobank"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"BSR20191601","DOI":"10.1042\/BSR20191601","article-title":"The roles of reactive oxygen species and antioxidants in cryopreservation","volume":"39","author":"Len","year":"2019","journal-title":"Biosci Rep"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"563","DOI":"10.3109\/09513591003686395","article-title":"Cryopreservation and oxidative stress in reproductive cells","volume":"26","author":"Tatone","year":"2010","journal-title":"Gynecol Endocrinol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.2047-2927.2013.00158.x","article-title":"Human semen cryopreservation: a sperm DNA fragmentation study with alkaline and neutral comet assay","volume":"2","author":"Ribas-Maynou","year":"2014","journal-title":"Andrology"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"654","DOI":"10.2164\/jandrol.05016","article-title":"Prevention of oxidative stress injury to sperm","volume":"26","author":"Agarwal","year":"2005","journal-title":"J Androl"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/aja.2010.182","article-title":"Antioxidant therapy in male infertility: fact or fiction?","volume":"13","author":"Zini","year":"2011","journal-title":"Asian J Androl"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1146\/annurev.arplant.55.031903.141701","article-title":"Reactive oxygen species: metabolism, oxidative stress, and signal transduction","volume":"55","author":"Apel","year":"2004","journal-title":"Annu Rev Plant Biol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"61","DOI":"10.5935\/1518-0557.20180003","article-title":"Review on the role of glutathione on oxidative stress and infertility","volume":"22","author":"Adeoye","year":"2018","journal-title":"JBRA Assist Reprod"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1017\/S0967199418000242","article-title":"Spermatic mitochondria: role in oxidative homeostasis, sperm function and possible tools for their assessment","volume":"26","author":"Losano","year":"2018","journal-title":"Zygote"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.jogoh.2018.06.008","article-title":"Reactive oxygen species in seminal plasma as a cause of male infertility","volume":"47","author":"Kumar","year":"2018","journal-title":"J Gynecol Obstet Hum Reprod"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3390\/antiox7100132","article-title":"Oxidative stress in the male germline: a review of novel strategies to reduce 4-hydroxynonenal production","volume":"7","author":"Walters","year":"2018","journal-title":"Antioxidants"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1095\/biolreprod.107.060558","article-title":"Polyunsaturated fatty acids in male and female reproduction","volume":"77","author":"Wathes","year":"2007","journal-title":"Biol Reprod"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/jeb.12275","article-title":"Effects of metabolic rate and sperm competition on the fatty-acid composition of mammalian sperm","volume":"27","author":"delBarco-Trillo","year":"2014","journal-title":"J Evol Biol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1111\/andr.12024","article-title":"Dietary fatty acids affect semen quality: a review","volume":"3","author":"Esmaeili","year":"2015","journal-title":"Andrology."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"96","DOI":"10.3390\/antiox8040096","article-title":"Water- and fat-soluble antioxidants in human seminal plasma and serum of fertile males","volume":"8","author":"Lazzarino","year":"2019","journal-title":"Antioxidants"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2013.02.011","article-title":"Reactive oxygen species and the free radical theory of aging","volume":"60","author":"Liochev","year":"2013","journal-title":"Free Radic Biol Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.reprotox.2010.11.010","article-title":"Effect of trans-resveratrol on induced oxidative stress in human sperm and in rat germinal cells","volume":"31","author":"Collodel","year":"2011","journal-title":"Reprod Toxicol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1177\/0394632015572080","article-title":"The protective effects of melatonin against cryopreservation-induced oxidative stress in human sperm","volume":"28","author":"Karimfar","year":"2015","journal-title":"Int J Immunopathol Pharmacol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.fertnstert.2012.05.001","article-title":"Sperm DNA fragmentation induced by cryopreservation: new insights and effect of a natural extract from Opuntia ficus-indica","volume":"98","author":"Meamar","year":"2012","journal-title":"Fertil Steril"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/j.fertnstert.2014.07.736","article-title":"Up-regulation of heme oxygenase-1 expression modulates reactive oxygen species level during the cryopreservation of human seminiferous tubules","volume":"102","author":"Tang","year":"2014","journal-title":"Fertil Steril"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"S84","DOI":"10.4103\/ijmr.IJMR_242_18","article-title":"Redox regulation and sperm function: a proteomic insight","volume":"148","author":"Mohanty","year":"2018","journal-title":"Indian J Med Res"},{"key":"ref33","first-page":"1775","article-title":"Glycolysis metabolic changes in sperm cryopreservation based on a targeted metabolomic strategy","volume":"12","author":"Fu","year":"2019","journal-title":"Int J Clin Exp Pathol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12894-019-0565-2","article-title":"Quantitative proteomic characterization of human sperm cryopreservation: using data-independent acquisition mass spectrometry","volume":"19","author":"Fu","year":"2019","journal-title":"BMC Urol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.cryobiol.2014.06.003","article-title":"A preliminary study on epigenetic changes during boar spermatozoa cryopreservation","volume":"69","author":"Zeng","year":"2014","journal-title":"Cryobiology"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.cryobiol.2003.09.003","article-title":"Hepatic cold hypoxia and oxidative stress: implications for ICAM-1 expression and modulation by glutathione during experimental isolated liver preservation","volume":"47","author":"El-Wahsh","year":"2003","journal-title":"Cryobiology"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.cryobiol.2003.10.008","article-title":"Strategies for exploration of freeze-responsive gene expression: advantages in vertebrate freeze tolerance","volume":"48","author":"Storey","year":"2004","journal-title":"Cryobiology"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1016\/j.freeradbiomed.2003.08.010","article-title":"In situ detection and localization of lipid peroxidation in individual bovine sperm cells","volume":"35","author":"Brouwers","year":"2003","journal-title":"Free Radic Biol Med"},{"key":"ref39","first-page":"963","article-title":"Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology","volume":"43","author":"Agarwal","year":"2005","journal-title":"Indian J Exp Biol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1387\/ijdb.072522bs","article-title":"Mammalian sperm metabolism: oxygen and sugar, friend and foe","volume":"52","author":"Storey","year":"2008","journal-title":"Int J Dev Biol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"R163","DOI":"10.1530\/REP-13-0178","article-title":"Mitochondria functionality and sperm quality","volume":"146","author":"Amaral","year":"2013","journal-title":"Reproduction"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1093\/humrep\/dep214","article-title":"Cryopreservation-induced human sperm DNA damage is predominantly mediated by oxidative stress rather than apoptosis","volume":"24","author":"Thomson","year":"2009","journal-title":"Hum Reprod"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3390\/antiox14040402","article-title":"The oxidative stress of human sperm cryopreservation","volume":"14","author":"Fleming","year":"2025","journal-title":"Antioxidants"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/1477-7827-12-112","article-title":"Utility of antioxidants during assisted reproductive techniques: an evidence-based review","volume":"12","author":"Agarwal","year":"2014","journal-title":"Reprod Biol Endocrinol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/aja.2012.144","article-title":"Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa","volume":"15","author":"Gavella","year":"2013","journal-title":"Asian J Androl"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"60","DOI":"10.5173\/ceju.2013.01.art19","article-title":"The role of oxidative stress and antioxidants in male fertility","volume":"65","author":"Walczak-Jedrzejowska","year":"2013","journal-title":"Cent European J Urol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1002\/iub.2008","article-title":"Vitamin E: regulatory redox interactions","volume":"71","author":"Miyazawa","year":"2019","journal-title":"IUBMB Life"},{"key":"ref48","first-page":"308","article-title":"Effect of semen extender supplementation with trehalose, vitamin C and E on post-thaw min pig sperm qualities","volume":"36","author":"Ma","year":"2015","journal-title":"Cryo Lett."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/S1472-6483(10)60254-4","article-title":"Effect of antioxidant supplementation of cryopreservation medium on post-thaw integrity of human spermatozoa","volume":"18","author":"Taylor","year":"2009","journal-title":"Reprod Biomed Online"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"e0145383","DOI":"10.1371\/journal.pone.0145383","article-title":"Vitamin E analogue improves rabbit sperm quality during cryopreservation through its antioxidative action","volume":"10","author":"Zhu","year":"2015","journal-title":"PLoS One"},{"key":"ref51","first-page":"113","article-title":"The complementary effect of cholesterol and vitamin E preloaded in cyclodextrins on frozen bovine semen: motility parameters, membrane integrity and lipid peroxidation","volume":"39","author":"Khellouf","year":"2018","journal-title":"Cryo Lett."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1111\/rda.13197","article-title":"Relation between respiratory activity and sperm parameters in boar spermatozoa cryopreserved with alpha-tocopherol and selected by Sephadex","volume":"53","author":"Satorre","year":"2018","journal-title":"Reprod Domest Anim"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.anireprosci.2016.09.011","article-title":"Effect of vitamin E and selenium nanoparticles on post-thaw variables and oxidative status of rooster semen","volume":"174","author":"Safa","year":"2016","journal-title":"Anim Reprod Sci"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/j.theriogenology.2016.03.038","article-title":"Effect of sperm concentration on characteristics and fertilization capacity of rooster sperm frozen in the presence of the antioxidants catalase and vitamin E","volume":"86","author":"Moghbeli","year":"2016","journal-title":"Theriogenology"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"e13543","DOI":"10.1111\/and.13543","article-title":"Alpha- and gamma-tocopherol levels in human semen and their potential functional implications","volume":"52","author":"Zerbinati","year":"2020","journal-title":"Andrologia"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.anireprosci.2014.01.011","article-title":"Role of melatonin on production and preservation of gametes and embryos: a brief review","volume":"145","author":"Cruz","year":"2014","journal-title":"Anim Reprod Sci"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/rda.12378","article-title":"Melatonin in sperm biology: breaking paradigms","volume":"49","author":"Cebri\u00e1n-P\u00e9rez","year":"2014","journal-title":"Reprod Domest Anim"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.cca.2015.04.029","article-title":"Melatonin and male reproduction","volume":"446","author":"Li","year":"2015","journal-title":"Clin Chim Acta"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/6472945","article-title":"Melatonin and caffeine supplementation used, respectively, as protective and stimulating agents in the cryopreservation of human sperm improves survival, viability, and motility after thawing compared to traditional TEST-yolk buffer","volume":"2019","author":"Pariz","year":"2019","journal-title":"Oxidative Med Cell Longev"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1016\/j.biopha.2018.11.075","article-title":"Resveratrol: from enhanced biosynthesis and bioavailability to multitargeting chronic diseases","volume":"109","author":"Pannu","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1111\/andr.12306","article-title":"Protective features of resveratrol on human spermatozoa cryopreservation may be mediated through 5' AMP-activated protein kinase activation","volume":"5","author":"Shabani Nashtaei","year":"2017","journal-title":"Andrology"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1016\/j.fertnstert.2010.01.058","article-title":"Effects of resveratrol supplementation on cryopreservation medium of human semen","volume":"94","author":"Garcez","year":"2010","journal-title":"Fertil Steril"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.cryobiol.2009.10.012","article-title":"Resveratrol and ascorbic acid prevent DNA damage induced by cryopreservation in human semen","volume":"60","author":"Branco","year":"2010","journal-title":"Cryobiology"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.freeradbiomed.2017.10.342","article-title":"Melatonin reduces oxidative damage and upregulates heat shock protein 90 expression in cryopreserved human semen","volume":"113","author":"Deng","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"ref65","first-page":"29","article-title":"Effects of tempol and quercetin on human sperm function after cryopreservation","volume":"38","author":"Azadi","year":"2017","journal-title":"Cryo Lett."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.bbrc.2008.11.130","article-title":"Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells","volume":"378","author":"Suchankova","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.nut.2016.09.008","article-title":"Role of nutraceutical SIRT1 modulators in AMPK and mTOR pathway: evidence of a synergistic effect","volume":"34","author":"Giovannini","year":"2017","journal-title":"Nutrition"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"e1938","DOI":"10.1097\/MD.0000000000001938","article-title":"Antioxidant effects of Brown algae Sargassum on sperm parameters: CONSORT-compliant article","volume":"94","author":"Sobhani","year":"2015","journal-title":"Medicine"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.neuropharm.2013.04.005","article-title":"BDNF-induced local protein synthesis and synaptic plasticity","volume":"76","author":"Leal","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"3943","DOI":"10.1210\/jc.2003-030196","article-title":"The human fetal testis is a site of expression of neurotrophins and their receptors: regulation of the germ cell and peritubular cell population","volume":"88","author":"Robinson","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s00418-006-0155-8","article-title":"The expression of neurotrophins and their receptors in the prenatal and adult human testis: evidence for functions in Leydig cells","volume":"126","author":"M\u00fcller","year":"2006","journal-title":"Histochem Cell Biol"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"4126","DOI":"10.1007\/s12035-015-9357-1","article-title":"Nuclear factor-kappaB-dependent sestrin2 induction mediates the antioxidant effects of BDNF against mitochondrial inhibition in rat cortical neurons","volume":"53","author":"Wu","year":"2016","journal-title":"Mol Neurobiol"},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.1111\/and.12601","article-title":"Effect of brain-derived neurotrophic factor on sperm function, oxidative stress and membrane integrity in human","volume":"49","author":"Najafi","year":"2017","journal-title":"Andrologia"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"437","DOI":"10.2164\/jandrol.109.007849","article-title":"Protective effects of ascorbate and catalase on human spermatozoa during cryopreservation","volume":"31","author":"Li","year":"2010","journal-title":"J Androl"},{"key":"ref75","first-page":"34","article-title":"Protective effects of glutathione supplementation against oxidative stress during cryopreservation of human spermatozoa","volume":"37","author":"Ghorbani","year":"2016","journal-title":"Cryo Lett"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.cryobiol.2017.12.009","article-title":"Mitochondria-targeted antioxidant MitoTEMPO improves the post-thaw sperm quality","volume":"80","author":"Lu","year":"2018","journal-title":"Cryobiology"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s10561-018-9731-0","article-title":"Supplementation of sperm freezing medium with myoinositol improves human sperm parameters and protects it against DNA fragmentation and apoptosis","volume":"20","author":"Mohammadi","year":"2019","journal-title":"Cell Tissue Bank"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.cryobiol.2020.03.011","article-title":"Elamipretide as a potential candidate for relieving cryodamage to human spermatozoa during cryopreservation","volume":"95","author":"Bai","year":"2020","journal-title":"Cryobiology"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1111\/and.12130","article-title":"Cryoprotective effect of L-carnitine on motility, vitality and DNA oxidation of human spermatozoa","volume":"46","author":"Banihani","year":"2014","journal-title":"Andrologia"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1071\/RD14118","article-title":"Stress preconditioning of semen before cryopreservation improves fertility and increases the number of offspring born: a prospective randomised study using a porcine model","volume":"28","author":"Horv\u00e1th","year":"2016","journal-title":"Reprod Fertil Dev"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1095\/biolreprod.110.083386","article-title":"Stress for stress tolerance? A fundamentally new approach in mammalian embryology","volume":"83","author":"Pribenszky","year":"2010","journal-title":"Biol Reprod"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1071\/RD10231","article-title":"Cells under pressure: how sublethal hydrostatic pressure stress treatment increases gametes\u2019 and embryos\u2019 performance","volume":"23","author":"Pribenszky","year":"2011","journal-title":"Reprod Fertil Dev"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1071\/RD13177","article-title":"Tolerance of spermatozoa to hypotonic stress: role of membrane fluidity and correlation with cryosurvival","volume":"27","author":"Oldenhof","year":"2015","journal-title":"Reprod Fertil Dev"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1870054\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:08:12Z","timestamp":1786968492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1870054\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":83,"alternative-id":["10.3389\/fmed.2026.1870054"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1870054","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"article-number":"1870054"}}