Effect of obesity on global sperm methylation and gene imprinting

Abstract

This study was to investigate whether high fat diet-induced obesity altered gene imprinting of sperm or global sperm DNA methylation. C57BL/6J mice at 3 week were fed on high fat diet (D12492) or control diet for 12 weeks. the mean weight of DIO mice was between 38 and 42g, mean weight of control diet mice was between 24 and 28g. With high fat diet-induced obese mouse model, differentially methylated region for imprinted gene and global genome methylation were bisulfite-sequenced. There were no significant differences between obese mouse group and control group: 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) and SNRPN(1.88% vs.3.13%;p=0.628). Moreover, methylation level of individual CG site at 8 imprinted gene was also not significantly changed(p>0.05). In addition, 8942 differentially methylated regions were detected across sperm genome. Gene enrichment analysis indicated that the most enrichment items were respectively metabolic process(n=1482), RNA synthesis(n=779) and transcription(n=767). Methylation level of imprinted gene may not be significantly altered in sperm from high fat-induced obese mouse, however, genes involved in metabolic process, RNA synthesis and transcription and so on might be significantly altered.