Orssaud Christophe, Barraud Lange Virginie, Wolf Jean Philippe, LeFoll Nathalie, Soufir Jean Claude
Functional Unit of Ophthalmology, Ophtara Rare disease Center, Sensgène Filière, ERN EYE, European Hospital Georges Pompidou, University Hospital Paris Centre, Assistance Publique de Hôpitaux de Paris, Paris, France.
Team Genomic Epigenetic and Physiopathology of Reproduction, Department of Genetic, Development and Cancer, Cochin Institute, Inserm U1016, Paris, France.
Front Neurol. 2023 Jan 4;13:946559. doi: 10.3389/fneur.2022.946559. eCollection 2022.
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.
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.
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.
我们报告了一名男性患者的精子特征，该患者18岁时患上了Leber遗传性视神经病变，这是一种由线粒体DNA突变以及核DNA变异导致的遗传性视神经病变。30岁时，他主诉不育已有2年。精液分析显示精子活力低，形态或超微结构异常的比例高。附睾标志物水平严重异常。艾地苯醌被用于治疗他的Leber遗传性视神经病变以提高视力。经过5个月的这种治疗，精子活力增加，其活力得到改善。自然受孕发生。
本病例首次描述了Leber遗传性视神经病变患者精子及附睾上皮的异常情况。它引起了人们对线粒体疾病患者精子病理学的关注。必须怀疑线粒体DNA突变的作用，因为它在精子的发育和活力中起着重要作用。此外，艾地苯醌可以绕过复合体I并将电子转移到复合体III。人们怀疑它对精子发生有有利影响。
本病例证实了Leber遗传性视神经病变中精子功能障碍的可能性，以及艾地苯醌作为治疗人类线粒体DNA突变所致不育症的价值。
