Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring (original) (raw)

methylation state of regulatory regions in spermatozoa (and oocytes) controls gene transcription in offspring. 7 Like many other cell types, mature spermatozoa in humans and rodents have high methylation levels at most repetitive elements and intergenic regions that transcriptionally repress these regions. Gene-specific hyper-or hypo-methylation is found at promoters, with a general observation of decreasing methylation with increasing CpG density. 8-12 Furthermore, the promoters of genes involved in early development are more likely to be hypo-methylated, suggesting that they are primed for activation in offspring. 10,12 Several studies have described alteration of normal sperm DNA methylation patterns, due to genotype, environmental exposure or disease. These include methylation changes associated with mutations in DNA methyltransferases, 13 reduced fertility, 14-17 toxin and drug exposure, 18-20 dietary alterations, 21,22 and stress exposure. 23,24 There is no sign of a "standard epigenetic response" to these insults, as increases and decreases in global and locus-specific DNA methylation have all been reported. An obstacle to the persistence of sperm methylation states in offspring is the extensive demethylation of the paternally-inherited chromosomes after fertilisation in humans and rodents. 25,26 Therefore,