Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility.
Recent evidence demonstrates a role for paternal aging on offspring disease susceptibility. It is well established that various neuropsychiatric disorders (schizophrenia, autism, etc.), trinucleotide expansion associated diseases (myotonic dystrophy, Huntington's, etc.) and even some forms of c...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-07-01
|
Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC4091790?pdf=render |
id |
doaj-ae3f77a707f34631980ecf0911fe0f17 |
---|---|
record_format |
Article |
spelling |
doaj-ae3f77a707f34631980ecf0911fe0f172020-11-25T01:11:53ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-07-01107e100445810.1371/journal.pgen.1004458Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility.Timothy G JenkinsKenneth I AstonChristian PfluegerBradley R CairnsDouglas T CarrellRecent evidence demonstrates a role for paternal aging on offspring disease susceptibility. It is well established that various neuropsychiatric disorders (schizophrenia, autism, etc.), trinucleotide expansion associated diseases (myotonic dystrophy, Huntington's, etc.) and even some forms of cancer have increased incidence in the offspring of older fathers. Despite strong epidemiological evidence that these alterations are more common in offspring sired by older fathers, in most cases the mechanisms that drive these processes are unclear. However, it is commonly believed that epigenetics, and specifically DNA methylation alterations, likely play a role. In this study we have investigated the impact of aging on DNA methylation in mature human sperm. Using a methylation array approach we evaluated changes to sperm DNA methylation patterns in 17 fertile donors by comparing the sperm methylome of 2 samples collected from each individual 9-19 years apart. With this design we have identified 139 regions that are significantly and consistently hypomethylated with age and 8 regions that are significantly hypermethylated with age. A representative subset of these alterations have been confirmed in an independent cohort. A total of 117 genes are associated with these regions of methylation alterations (promoter or gene body). Intriguingly, a portion of the age-related changes in sperm DNA methylation are located at genes previously associated with schizophrenia and bipolar disorder. While our data does not establish a causative relationship, it does raise the possibility that the age-associated methylation of the candidate genes that we observe in sperm might contribute to the increased incidence of neuropsychiatric and other disorders in the offspring of older males. However, further study is required to determine whether, and to what extent, a causative relationship exists.http://europepmc.org/articles/PMC4091790?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Timothy G Jenkins Kenneth I Aston Christian Pflueger Bradley R Cairns Douglas T Carrell |
spellingShingle |
Timothy G Jenkins Kenneth I Aston Christian Pflueger Bradley R Cairns Douglas T Carrell Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genetics |
author_facet |
Timothy G Jenkins Kenneth I Aston Christian Pflueger Bradley R Cairns Douglas T Carrell |
author_sort |
Timothy G Jenkins |
title |
Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. |
title_short |
Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. |
title_full |
Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. |
title_fullStr |
Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. |
title_full_unstemmed |
Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. |
title_sort |
age-associated sperm dna methylation alterations: possible implications in offspring disease susceptibility. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2014-07-01 |
description |
Recent evidence demonstrates a role for paternal aging on offspring disease susceptibility. It is well established that various neuropsychiatric disorders (schizophrenia, autism, etc.), trinucleotide expansion associated diseases (myotonic dystrophy, Huntington's, etc.) and even some forms of cancer have increased incidence in the offspring of older fathers. Despite strong epidemiological evidence that these alterations are more common in offspring sired by older fathers, in most cases the mechanisms that drive these processes are unclear. However, it is commonly believed that epigenetics, and specifically DNA methylation alterations, likely play a role. In this study we have investigated the impact of aging on DNA methylation in mature human sperm. Using a methylation array approach we evaluated changes to sperm DNA methylation patterns in 17 fertile donors by comparing the sperm methylome of 2 samples collected from each individual 9-19 years apart. With this design we have identified 139 regions that are significantly and consistently hypomethylated with age and 8 regions that are significantly hypermethylated with age. A representative subset of these alterations have been confirmed in an independent cohort. A total of 117 genes are associated with these regions of methylation alterations (promoter or gene body). Intriguingly, a portion of the age-related changes in sperm DNA methylation are located at genes previously associated with schizophrenia and bipolar disorder. While our data does not establish a causative relationship, it does raise the possibility that the age-associated methylation of the candidate genes that we observe in sperm might contribute to the increased incidence of neuropsychiatric and other disorders in the offspring of older males. However, further study is required to determine whether, and to what extent, a causative relationship exists. |
url |
http://europepmc.org/articles/PMC4091790?pdf=render |
work_keys_str_mv |
AT timothygjenkins ageassociatedspermdnamethylationalterationspossibleimplicationsinoffspringdiseasesusceptibility AT kennethiaston ageassociatedspermdnamethylationalterationspossibleimplicationsinoffspringdiseasesusceptibility AT christianpflueger ageassociatedspermdnamethylationalterationspossibleimplicationsinoffspringdiseasesusceptibility AT bradleyrcairns ageassociatedspermdnamethylationalterationspossibleimplicationsinoffspringdiseasesusceptibility AT douglastcarrell ageassociatedspermdnamethylationalterationspossibleimplicationsinoffspringdiseasesusceptibility |
_version_ |
1725169025117323264 |