肥胖对小鼠精子全基因组DNA甲基化以及基因印迹的影响  

Effects of obesity on global genome DNA methylation and gene imprinting in mouse spermatozoa

作　　者：朱锦亮[1] 吴银玲[2] 唐文豪[3] 田园[2] 葛少钦[2] 刘平[1] 乔杰[1] 

机构地区：[1]北京大学第三医院妇产科生殖医学中心,北京100191 [2]河北大学医学部,河北保定071000 [3]北京大学第三医院泌尿外科,北京100191

出　　处：《中华男科学杂志》2017年第6期488-496,共9页National Journal of Andrology

基　　金：国家自然科学基金青年基金(81300483)~~

摘　　要：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 the influence of high fat diet-induced obesity （ HFDIO ） on the differentially methylated region （DMR） of the imprinted gene and global genome methylation of sperm DNA. Methods ： We performed bisulfite sequencing on the DMR of the imprinted gene and global genome methylation of sperm DNA in the mouse model of HFDIO. Results ： No statistically significant differences were found between the HFDIO model and normal control mice in MEG3-IC （93.73 vs 97. 26%, P = 0.252 ） , H19 （98.00vs97.83%, P = 0.920）, IGF2 （97.34vs96.25%, P =0.166）, IGF2R （1.43 vs 1.11%, P = 0.695）, PEC3 （0.19 vs 0, 38% , P = 0.537）, MEST （ 0. 23 vs 0. 68% , P = 0.315）, NNAT （ 0. 31vs 0. 00% , P = 0.134）, orSNRPN （1.88 vs 3.13% , P = 0. 628）. A total of 8 942 DMRs were detected across the sperm genome （P 〈 0.05）. Gene functional enrichment analysis indicated that the enriched terms with the largest numbers of genes were the metabolic process （n = 1 482）, RNA synthesis（ n = 779 ）, and transcription （ n = 767 ）. Conclusion ： The methylation level underwent no significant change in the DMRs of the imprinted genes from the mice with HFDIO, but the CG methylation of the genes involved in the metabolic process, RNA synthesis and transcription were significantly altered.

关 键 词：肥胖 精子 基因印迹 全基因组甲基化 

分 类 号：R589.2[医药卫生—内分泌]