{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:09:42Z","timestamp":1753891782411,"version":"3.41.2"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"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. Neurol."],"abstract":"<jats:sec><jats:title>Case<\/jats:title><jats:p>We report the sperm characteristics of a male patient who developed, when he was 18 years old, a Leber hereditary optic neuropathy, a hereditary optic neuropathy due to mtDNA mutation as well as variants in the nuclear DNA. At the age of 30 years-old, he complained of infertility lasting for 2 years. Semen analyses showed low motility spermatozoa and a high percentage of morphological or ultrastructural abnormalities. Levels of epididymal markers were strongly atypical. Idebenone was prescribed as treatment of his Leber hereditary optic neuropathy in order to improve his visual acuity. After 5 months of this treatment, motility of spermatozoa increased, and their vitality improved. A natural conception occurred.<\/jats:p><\/jats:sec><jats:sec><jats:title>Outcome<\/jats:title><jats:p>This case is the first description of an anomaly of spermatozoas and of the epididymis epithelium in a patient with Leber hereditary optic neuropathy. It draws attention to sperm pathologies in patients with mitochondrial disorders. The role of the mtDNA mutations must be suspected since it plays an important role in the development and motility of spermatozoa. In addition, idebenone can by-pass the complex I and transfer electrons to complex III. It has been suspected to have a favorable effect on spermatogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case confirms the possibility of sperm dysfunction in Leber hereditary optic neuropathy and the interest of idebenone as a treatment for infertility due to mtDNA mutations in human.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.946559","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T12:24:54Z","timestamp":1672835094000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Abnormalities of sperm motility and morphology in a patient with Leber hereditary optic neuropathy: Improvement after idebenone therapy"],"prefix":"10.3389","volume":"13","author":[{"given":"Christophe","family":"Orssaud","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginie","family":"Barraud Lange","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Philippe","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"LeFoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Claude","family":"Soufir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s100480100115","article-title":"Leber hereditary optic neuropathy: clinical and molecular genetic findings","volume":"3","author":"Huoponen","year":"2001","journal-title":"Neurogenetics."},{"key":"B2","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1002\/ana.20236","article-title":"The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic neuropathy","volume":"56","author":"Valentino","year":"2004","journal-title":"Ann Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3390\/genes12040521","article-title":"MCAT mutations cause nuclear LHON-like optic neuropathy","volume":"12","author":"Gerber","year":"2021","journal-title":"Genes."},{"key":"B4","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1097\/WNO.0000000000000623","article-title":"Cardiac disorders in patients with Leber hereditary optic neuropathy","volume":"38","author":"Orssaud","year":"2018","journal-title":"J Neuroophthalmol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"651639","DOI":"10.3389\/fneur.2021.651639","article-title":"Leber hereditary optic neuropathy: review of treatment and management","volume":"12","author":"Hage","year":"2021","journal-title":"Front Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"662838","DOI":"10.3389\/fneur.2021.662838","article-title":"Intravitreal gene therapy vs. natural history in patients with leber hereditary optic neuropathy carrying them 11778G>A ND4 mutation: systematic review and indirect comparison","volume":"12","author":"Newman","year":"2021","journal-title":"Front Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1093\/molehr\/8.8.719","article-title":"Can mitochondrial DNA mutations cause sperm dysfunction?","volume":"8","author":"Spiropoulos","year":"2002","journal-title":"Mol Hum Reprod."},{"key":"B8","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1093\/humupd\/dmab001","article-title":"Mitochondria: their role in spermatozoa and in male infertility","volume":"27","author":"Boguenet","year":"2021","journal-title":"Hum Reprod."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.3390\/antiox10071079","article-title":"Improving sperm oxidative stress and embryo quality in advanced paternal age using idebenone in vitro: a proof-of-concept study","volume":"10","author":"Nikitaras","year":"2021","journal-title":"Antioxidants."},{"key":"B10","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cryobiol.2019.09.004","article-title":"Idebenone improves quality of ram sperm by mitigating oxidative stress during cryopreservation","volume":"90","author":"Lone","year":"2019","journal-title":"Cryobiology."},{"key":"B11","first-page":"146","article-title":"Effect of idebenone, resveratrol and taurine on the sperm quality and lipid peroxidation of cryopreserved crossbred ram semen","volume":"42","author":"Lone","year":"2021","journal-title":"Cryo Lett."},{"key":"B12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.mito.2017.01.004","article-title":"Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy","volume":"36","author":"Yu-Wai-Man","year":"2017","journal-title":"Mitochondrion."},{"key":"B13","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/00041327-200020030-00006","article-title":"Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy?","volume":"20","author":"Mashima","year":"2000","journal-title":"J Neuro-Ophthalmol Off J N Am Neuro-Ophthalmol Soc."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.3390\/antiox11061152","article-title":"Antioxidants and male infertility","volume":"11","author":"Silva","year":"2022","journal-title":"Antioxidants."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1007\/s12031-020-01729-y","article-title":"Oxidative stress profile in genetically confirmed cases of Leber's hereditary optic neuropathy","volume":"71","author":"Rovcanin","year":"2021","journal-title":"J Mol Neurosci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"917348","DOI":"10.3389\/fnins.2022.917348","article-title":"Superoxide dismutase 2 ameliorates mitochondrial dysfunction in skin fibroblasts of Leber's hereditary optic neuropathy patients","volume":"16","author":"Zhou","year":"2022","journal-title":"Front Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.devcel.2005.01.021","article-title":"The Sept4 septin locus is required for sperm terminal differentiation in mice","volume":"8","author":"Kissel","year":"2005","journal-title":"Dev Cell."},{"key":"B18","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.fertnstert.2005.12.042","article-title":"New fibrous sheath anomaly in spermatozoa of men with consanguinity","volume":"86","author":"Escalier","year":"2006","journal-title":"Fertil Steril."},{"key":"B19","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1086\/303040","article-title":"Human mtDNA haplogroups associated with high or reduced spermatozoa motility","volume":"67","author":"Ruiz-Pesini","year":"2000","journal-title":"Am J Hum Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1093\/humrep\/dep017","article-title":"Coiled sperm from infertile patients: characteristics, associated factors and biological implication","volume":"24","author":"Yeung","year":"2009","journal-title":"Hum Reprod."},{"key":"B21","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3109\/14647273.2015.1050462","article-title":"Oral antioxidant treatment partly improves integrity of human sperm DNA in infertile grade I varicocele patients","volume":"18","author":"Gual-Frau","year":"2015","journal-title":"Hum Fertil."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1007\/s10815-013-0047-5","article-title":"Coenzyme Q10 and male infertility: a meta-analysis","volume":"30","author":"Lafuente","year":"2013","journal-title":"J Assist Reprod Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.redox.2015.01.009","article-title":"Border between natural product and drug: comparison of the related benzoquinones idebenone and coenzyme Q10","volume":"4","author":"Gueven","year":"2015","journal-title":"Redox Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.pharep.2015.07.005","article-title":"Nuclear factor E2-related factor-2 (Nrf2) expression and regulation in male reproductive tract","volume":"68","author":"Wajda","year":"2016","journal-title":"Pharmacol Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"3503","DOI":"10.3390\/jcm10163503","article-title":"Using data mining to assist in predicting reproductive outcomes following varicocele embolization","volume":"10","author":"Sousa","year":"2021","journal-title":"J Clin Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.rbmo.2022.07.004","article-title":"Revisiting the impact of varicocele and its treatments on male fertility","volume":"45","author":"Lewis","year":"2022","journal-title":"Reprod Biomed."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1093\/jn\/nxz149","article-title":"Men's intake of vitamin C and \u03b2-carotene is positively related to fertilization rate but not to live birth rate in couples undergoing infertility treatment","volume":"149","author":"Li","year":"2019","journal-title":"J Nutr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.bbrc.2018.03.120","article-title":"Ascorbic acid as DNase I inhibitor in prevention of male infertility","volume":"498","author":"Ili\u0107","year":"2018","journal-title":"Biochem Biophys Res Commun."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.946559\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T12:24:56Z","timestamp":1672835096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.946559\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":28,"alternative-id":["10.3389\/fneur.2022.946559"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.946559","relation":{},"ISSN":["1664-2295"],"issn-type":[{"type":"electronic","value":"1664-2295"}],"subject":[],"published":{"date-parts":[[2023,1,4]]},"article-number":"946559"}}