Varicocele pathophysiology is related to increased oxidative stress, which might result in loss sperm DNA integrity as well as in genomic instability. Sperm telomere shortening and loss of global DNA methylation are the main features of genomic instability, leading to cell senescence and death, whereas sperm DNA fragmentation (SDF) characterizes the loss of chromatin integrity. We hypothesize that sperm genomic stability and DNA integrity is reduced in infertile men with moderate and large-sized varicoceles, thus being candidate markers of sperm quality in varicocele-related infertility. Here, we assessed the sperm global DNA methylation, telomere length, and SDF in men with and without clinically palpable varicoceles. While the rates of SDF and telomere length were not statistically different between varicocele patients and controls, global sperm DNA methylation seems to be lower in men with varicocele (49.7% ± 20.7%) than controls (64.7% ± 17.1%). A negative correlation between SDF and sperm motility and a positive correlation between sperm morphology and telomere length were observed. Our results suggest that varicocele may result in genomic instability, in particular, global DNA hypomethylation. However, a large sample size may confirm these findings. The understanding of the molecular mechanisms involved in the pathophysiology of varicocele-related infertility may help to better select candidates for varicocele repair.

精索静脉曲张的病理生理学与氧化应激的增加有关，氧化应激可能导致精子DNA完整性丧失以及基因组不稳定。精子端粒的缩短和整体DNA甲基化的丧失是基因组不稳定的主要特征，导致细胞衰老和死亡，而精子DNA片段化（SDF）则表征了染色质完整性的丧失。我们假设中，大型精索静脉曲张的不育男性精子基因组稳定性和DNA完整性降低，因此是精索静脉曲张相关性不育症中精子质量的候选标记。在这里，我们评估了有或没有临床上可触及的精索静脉曲张的男性的精子整体DNA甲基化，端粒长度和SDF。尽管精索静脉曲张患者和对照组的SDF率和端粒长度无统计学差异，精索静脉曲张（49.7％±20.7％）的男性的整体精子DNA甲基化似乎低于对照组（64.7％±17.1％）。观察到SDF与精子活力呈负相关，而精子形态与端粒长度呈正相关。我们的结果表明精索静脉曲张可能导致基因组不稳定，特别是总体DNA甲基化不足。但是，大样本量可能会证实这些发现。对精索静脉曲张相关性不育症的病理生理学所涉及的分子机制的了解可能有助于更好地选择精索静脉曲张修复的候选人。我们的结果表明精索静脉曲张可能导致基因组不稳定，特别是总体DNA甲基化不足。但是，大样本量可能会证实这些发现。对精索静脉曲张相关性不育症的病理生理学所涉及的分子机制的了解可能有助于更好地选择精索静脉曲张修复的候选人。我们的结果表明精索静脉曲张可能导致基因组不稳定，特别是总体DNA甲基化不足。但是，大样本量可能会证实这些发现。对精索静脉曲张相关性不育症的病理生理学所涉及的分子机制的了解可能有助于更好地选择精索静脉曲张修复的候选人。