Montjean D, Zini A, Ravel C, Belloc S, Dalleac A, Copin H, Boyer P, McElreavey K, Benkhalifa M
Service de Medicine et Biologie de la Reproduction, Hopital Saint-Joseph, Marseille, France.
Andrology. 2015 Mar;3(2):235-40. doi: 10.1111/andr.12001. Epub 2015 Mar 6.
Sperm DNA methylation abnormalities have been detected in oligozoospermic men. However, the association between sperm DNA methylation defects, sperm parameters and sperm DNA, and chromatin integrity remains poorly understood. This study was designed to clarify this issue. We recruited a cohort of 92 men (62 normozoospermic and 30 oligoasthenozoospermic) presenting for infertility evaluation during a 1-year period. Sperm global DNA methylation was evaluated by an ELISA-like method, DNA fragmentation was evaluated by flow cytometry-based terminal transferase dUTP nick end-labeling (TUNEL) assay (reported as DNA fragmentation index or DFI), and sperm denaturation was evaluated by aniline blue staining (reported as sperm denaturation index or SDI, a marker of chromatin compaction). We found a significant positive association between sperm global DNA methylation level and conventional sperm parameters (sperm concentration and motility), supported by the results of methylation analysis on H19-DMR. We also identified significant inverse relationships between sperm global DNA methylation, and, both DFI and SDI. However, sperm global DNA methylation level was not related to sperm vitality or morphology. Our findings suggest that global sperm DNA methylation levels are related to conventional sperm parameters, as well as, sperm chromatin and DNA integrity.
在少精子症男性中已检测到精子DNA甲基化异常。然而，精子DNA甲基化缺陷、精子参数与精子DNA及染色质完整性之间的关联仍知之甚少。本研究旨在阐明这一问题。我们招募了一组92名男性（62名正常精子症患者和30名少弱精子症患者），他们在1年期间前来进行不孕评估。采用类似酶联免疫吸附测定（ELISA）的方法评估精子整体DNA甲基化，通过基于流式细胞术的末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）测定评估DNA片段化（报告为DNA片段化指数或DFI），并通过苯胺蓝染色评估精子变性（报告为精子变性指数或SDI，染色质压实的标志物）。我们发现精子整体DNA甲基化水平与传统精子参数（精子浓度和活力）之间存在显著正相关，这得到了H19-DMR甲基化分析结果的支持。我们还发现精子整体DNA甲基化与DFI和SDI均存在显著负相关。然而，精子整体DNA甲基化水平与精子活力或形态无关。我们的研究结果表明，精子整体DNA甲基化水平与传统精子参数以及精子染色质和DNA完整性有关。
