活性氧诱导的 H19-Igf2 甲基化模式、精液代谢产物和精液质量的改变。
Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality.
机构信息
Department of Embryology and Andrology, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, 1936773493, Iran.
American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, 44195, USA.
出版信息
J Assist Reprod Genet. 2019 Feb;36(2):241-253. doi: 10.1007/s10815-018-1350-y. Epub 2018 Oct 31.
PURPOSE
This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.
METHODS
Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/10 sperm]: group 1 (n = 39): low (ROS < 20), group 2 (n = 38): mild (20 ≤ ROS < 40), group 3 (n = 31): moderate (40 ≤ ROS < 60), and group 4 (n = 43): high (ROS ≥ 60). A comprehensive analysis of SP and semen parameters, including conventional semen characteristics, measurement of total antioxidant capacity (TAC), sperm DNA fragmentation index (DFI), chromatin maturation index (CMI), H19-Igf2 methylation status, and untargeted seminal metabolic profiling using nuclear magnetic resonance spectroscopy (1H-NMR), was carried out.
RESULT(S): The methylation status of H19 and Igf2 was significantly different in specimens with high ROS (P < 0.005). Metabolic fingerprinting of these SP samples showed upregulation of trimethylamine N-oxide (P < 0.001) and downregulations of tryptophan (P < 0.05) and tyrosine/tyrosol (P < 0.01). High ROS significantly reduced total sperm motility (P < 0.05), sperm concentration (P < 0.001), and seminal TAC (P < 0.001) but increased CMI and DFI (P < 0.005). ROS levels have a positive correlation with Igf2 methylation (r = 0.19, P < 0.05), DFI (r = 0.40, P < 0.001), CMI (r = 0.39, P < 0.001), and trimethylamine N-oxide (r = 0.45, P < 0.05) and a negative correlation with H19 methylation (r = - 0.20, P < 0.05), tryptophan (r = - 0.45, P < 0.05), sperm motility (r = - 0.20, P < 0.05), sperm viability (r = - 0.23, P < 0.01), and sperm concentration (r = - 0.30, P < 0.001).
CONCLUSION(S): Results showed significant correlation between ROS levels and H19-Igf2 gene methylation as well as semen parameters. These findings are critical to identify idiopathic male infertility and its management through assisted reproduction technology (ART).
目的
本研究旨在探讨活性氧（ROS）水平对精液（SP）代谢环境和精子功能障碍的影响。
方法
对 151 例正常精子症男性的精液标本进行化学发光法 ROS 检测，并根据 ROS 水平[相对光单位（RLU）/s/10 精子]进行分组：第 1 组（n=39）：低（ROS<20）；第 2 组（n=38）：轻度（20≤ROS<40）；第 3 组（n=31）：中度（40≤ROS<60）；第 4 组（n=43）：高（ROS≥60）。对 SP 和精液参数进行综合分析，包括常规精液特征、总抗氧化能力（TAC）测量、精子 DNA 碎片指数（DFI）、染色质成熟指数（CMI）、H19-Igf2 甲基化状态，以及使用核磁共振波谱（1H-NMR）进行非靶向性精液代谢特征分析。
结果
高 ROS 组的 H19 和 Igf2 甲基化状态差异显著（P<0.005）。这些 SP 样本的代谢指纹图谱显示，氧化三甲胺（TMAO）上调（P<0.001），色氨酸（Trp）和酪氨酸/tyrosol 下调（P<0.01）。高 ROS 显著降低总精子活力（P<0.05）、精子浓度（P<0.001）和 SP 总抗氧化能力（TAC）（P<0.001），但增加 CMI 和 DFI（P<0.005）。ROS 水平与 Igf2 甲基化（r=0.19，P<0.05）、DFI（r=0.40，P<0.001）、CMI（r=0.39，P<0.001）和 TMAO（r=0.45，P<0.05）呈正相关，与 H19 甲基化（r=-0.20，P<0.05）、色氨酸（r=-0.45，P<0.05）、精子活力（r=-0.20，P<0.05）、精子存活率（r=-0.23，P<0.01）和精子浓度（r=-0.30，P<0.001）呈负相关。
结论
结果表明，ROS 水平与 H19-Igf2 基因甲基化以及精液参数之间存在显著相关性。这些发现对于通过辅助生殖技术（ART）来识别特发性男性不育症及其管理至关重要。
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