title: Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring.
abstract: There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is: do changes in sperm DNA methylation have phenotypic consequences for offspring? We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating (16-19 weeks old, n = 14/14). A small (0.25%) increase in total 5-methyl-2Ͳ-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyl-CpG binding domain protein-enriched genome sequencing (MBD-Seq) and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers (both groups from n = 8 fathers) revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Youngson
authors.affiliation: Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lecomte
authors.affiliation: Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maloney
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Preston
authors.initials: P
authors.lastname: Leung
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Luke B
authors.initials: LB
authors.lastname: Hesson
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Fabio
authors.initials: F
authors.lastname: Luciani
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.|University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, 37 Kent Street Woolloongabba, Queensland 4102, Australia.
authors.forename: Lutz
authors.initials: L
authors.lastname: Krause
authors.affiliation: Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D016678:Genome; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013094:Spermatozoa / Q000378:metabolism*