Institut Pasteur, Unité de Génétique du Développement Humain, Paris, France; Laboratoire d'Eylau, Unilabs, Paris, France.
Fertil Steril. 2013 Nov;100(5):1241-7. doi: 10.1016/j.fertnstert.2013.06.047. Epub 2013 Aug 2.
To characterize a potential genetic cause for methylation errors described in oligozoospermia.
Analysis of PEG1/MEST-DMR and H19-DMR methylation level in sperm, in parallel with the study of several genes on the Y chromosome, DNMT3A, and DNMT3L. Clinical outcome was also looked at regarding PEG1/MEST-DMR and H19-DMR methylation level in sperm.
Research and diagnostic laboratories.
PATIENT(S): One hundred nineteen normospermic and 175 oligozoospermic men consulting for couple infertility.
INTERVENTION(S): We studied PEG1/MEST-DMR and H19-DMR methylation profiles in 294 men. We searched for Y chromosome gene aberrations and for mutations in both DNMT3A and DNMT3L genes in men showing epimutations. Assisted reproductive technology (ART) outcomes were also investigated.
MAIN OUTCOME MEASURE(S): Sperm samples were collected from 294 volunteers for genomic DNA isolation that was used to study methylation profiles in imprinted loci and Y chromosome SMCY, DNMT3A, and DNMT3L genes. Pregnancy rate was also studied after ART treatment using sperm showing epimutations.
RESULT(S): Epimutations in H19-DMR and PEG1/MEST-DMR were found in 20% and 3% of oligozoospermic men, respectively. We identified an amino acid change in DNMT3A in one case and in DNMT3L in eight men with altered methylation profiles. No mutations were detected in SMCY or in selected Y chromsome genes. No correlation between ART outcome and epimutations was found.
CONCLUSION(S): We observed epimethylations in spermatozoa of oligozoospermic individuals, but no association was found with genetic variants or in the ART outcome.
描述少精子症中描述的甲基化错误的潜在遗传原因。
分析精子中 PEG1/MEST-DMR 和 H19-DMR 的甲基化水平，同时研究 Y 染色体上的几个基因、DNMT3A 和 DNMT3L。还观察了精子中 PEG1/MEST-DMR 和 H19-DMR 甲基化水平的临床结局。
研究和诊断实验室。
119 名正常精子和 175 名少精子症男性，因夫妇不育就诊。
我们研究了 294 名男性的 PEG1/MEST-DMR 和 H19-DMR 甲基化谱。我们在显示表观遗传的男性中寻找 Y 染色体基因异常和 DNMT3A 和 DNMT3L 基因的突变。还研究了辅助生殖技术（ART）的结果。
从 294 名志愿者采集精子样本进行基因组 DNA 分离，用于研究印迹基因座和 Y 染色体 SMCY、DNMT3A 和 DNMT3L 基因的甲基化谱。还研究了 ART 治疗后使用显示表观遗传的精子的妊娠率。
在少精子症男性中，H19-DMR 和 PEG1/MEST-DMR 的表观遗传分别发现了 20%和 3%。我们在一个有改变的甲基化谱的病例中发现了 DNMT3A 的氨基酸变化，在 8 个男性中发现了 DNMT3L 的氨基酸变化。在 SMCY 或选定的 Y 染色体基因中未检测到突变。ART 结果与表观遗传无相关性。
我们观察到少精子症个体精子中的表观甲基化，但未发现与遗传变异或 ART 结果相关。
