Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring

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...

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Main Authors: Neil A Youngson, Virginie Lecomte, Christopher A Maloney, Preston Leung, Jia Liu, Luke B Hesson, Fabio Luciani, Lutz Krause, Margaret J Morris
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2016-01-01
Series:Asian Journal of Andrology
Subjects:
Online Access:http://www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume=18;issue=6;spage=930;epage=936;aulast=Youngson
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author Neil A Youngson
Virginie Lecomte
Christopher A Maloney
Preston Leung
Jia Liu
Luke B Hesson
Fabio Luciani
Lutz Krause
Margaret J Morris
author_facet Neil A Youngson
Virginie Lecomte
Christopher A Maloney
Preston Leung
Jia Liu
Luke B Hesson
Fabio Luciani
Lutz Krause
Margaret J Morris
author_sort Neil A Youngson
collection DOAJ
description 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.
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spelling doaj.art-0ed6e12b3ceb408b94b78873d07da8182022-12-22T03:38:43ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X1745-72622016-01-0118693093610.4103/1008-682X.163190Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspringNeil A YoungsonVirginie LecomteChristopher A MaloneyPreston LeungJia LiuLuke B HessonFabio LucianiLutz KrauseMargaret J MorrisThere 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.http://www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume=18;issue=6;spage=930;epage=936;aulast=Youngsonmethylation; obesity; spermatozoa
spellingShingle Neil A Youngson
Virginie Lecomte
Christopher A Maloney
Preston Leung
Jia Liu
Luke B Hesson
Fabio Luciani
Lutz Krause
Margaret J Morris
Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring
Asian Journal of Andrology
methylation; obesity; spermatozoa
title Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring
title_full Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring
title_fullStr Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring
title_full_unstemmed Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring
title_short Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring
title_sort obesity induced sperm dna methylation changes at satellite repeats are reprogrammed in rat offspring
topic methylation; obesity; spermatozoa
url http://www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume=18;issue=6;spage=930;epage=936;aulast=Youngson
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