Santana Viviane Paiva, Miranda-Furtado Cristiana Libardi, Pedroso Daiana Cristina Chielli, Eiras Matheus Credendio, Vasconcelos Maria Aparecida Carneiro, Ramos Ester Silveira, Calado Rodrigo Tocantins, Ferriani Rui Alberto, Esteves Sandro Cassiano, Dos Reis Rosana Maria
a Department of Gynecology and Obstetrics, Ribeirão Preto Medical School , University of São Paulo , Ribeirão Preto, São Paulo , Brazil.
b Department of Genetics, Ribeirão Preto Medical School , University of São Paulo , Ribeirão Preto, São Paulo , Brazil.
Syst Biol Reprod Med. 2019 Apr;65(2):95-104. doi: 10.1080/19396368.2018.1557762. Epub 2019 Jan 2.
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增加有关，这可能导致精子DNA完整性丧失以及基因组不稳定。精子端粒缩短和整体DNA甲基化缺失是基因组不稳定的主要特征，会导致细胞衰老和死亡，而精子DNA片段化（SDF）则是染色质完整性丧失的特征。我们假设，患有中度和大型精索静脉曲张的不育男性的精子基因组稳定性和DNA完整性会降低，因此是精索静脉曲张相关性不育中精子质量的候选标志物。在此，我们评估了有和没有临床可触及精索静脉曲张的男性的精子整体DNA甲基化、端粒长度和SDF。虽然精索静脉曲张患者和对照组之间的SDF率和端粒长度没有统计学差异，但精索静脉曲张男性的精子整体DNA甲基化似乎低于对照组（49.7%±20.7%）（对照组为64.7%±17.1%）。观察到SDF与精子活力之间呈负相关，精子形态与端粒长度之间呈正相关。我们的结果表明，精索静脉曲张可能导致基因组不稳定,特别是整体DNA低甲基化。然而，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病理生理学中涉及的分子机制的理解可能有助于更好地选择精索静脉曲张修复的候选者。
