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目的:研究高脂饲料诱导的肥胖是否影响小鼠精子印迹基因差异甲基化区域和精子全基因组DNA甲基化水平。方法:利用高脂饲料诱导的肥胖小鼠模型,进行精子DNA的全基因组甲基化和印迹基因差异甲基化区测序。结果:高脂饲料诱导的肥胖组印迹基因差异甲基化区甲基化水平与普通饲料对照组无显著差异:MEG3-IG(93.73%vs 97.26%;P=0.252),H19(98.00%vs 97.83%,P=0.920),IGF2(97.34%vs 96.25%,P=0.166),IGF2R(1.43%vs 1.11%,P=0.695),PEG3(0.19%vs 0.38%,P=0.537),MEST(0.23%vs 0.68%,P=0.315),NNAT(0.31%vs 0.00%,P=0.134)和SNRPN(1.88%vs 3.13%,P=0.628)。精子全基因组范围内总共发现8 942个甲基化有显著差异的区域(P<0.05)。对差异甲基化区域进行基因功能富集,富集基因数目最多的3项分别为代谢(n=1 482),RNA合成(n=779)和转录(n=767)。结论:高脂饲料诱导的肥胖小鼠精子印迹基因差异甲基化区甲基化水平没有发生显著改变,参与代谢、RNA合成以及转录过程基因CG序列甲基化显著改变。
OBJECTIVE: To investigate whether obesity induced by high-fat diet affects methylation of spermatozoa imprinted genes and methylation of whole genome DNA of sperm in mice. Methods: Fat mouse model induced by high-fat diet was used to carry out whole-genome methylation of sperm DNA and differential methylation region sequencing of imprinted genes. Results: There was no significant difference in the methylation level of methylation of imprinted genes in obese rats induced by high-fat diet compared with the control group: MEG3-IG (93.73% vs 97.26%; P = 0.252), H19 (98.00% vs 97.83 IGF2R (1.43% vs 1.11%, P = 0.695), PEG3 (0.19% vs 0.38%, P = 0.537), MEST (0.23% vs 0.38% vs 0.68%, P = 0.315), NNAT (0.31% vs 0.00%, P = 0.134) and SNRPN (1.88% vs 3.13%, P = 0.628). A total of 8 942 methylated significant regions were found in the whole genome of sperm (P <0.05). Gene enrichment was carried out on differentially methylated regions. The three genes with the largest number of genes were metabolic (n = 1 482), RNA synthesis (n = 779) and transcription (n = 767), respectively. Conclusion: There is no significant change in the methylation level of spermatogenic imprinted genes in obese mice induced by high-fat diet. Metabolism, RNA synthesis and methylation of gene CG sequences in transcription process are significantly changed.