Age-Associated Alterations to Sperm DNA Methylation and Possible Consequences on the Offspring

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Publication Type dissertation
School or College School of Medicine
Department Physiology
Author Jenkins, Timothy Gerald
Title Age-Associated Alterations to Sperm DNA Methylation and Possible Consequences on the Offspring
Date 2013-12
Description The effects of advanced paternal age have received little attention in the past. However, recent data from multiple groups suggesting an association between advanced paternal age and various disorders in the offspring have sparked a great deal of interest. Specifically, offspring of older fathers have an increased risk of autism, bipolar disorder, and schizophrenia among other issues. Further fueling this interest is the striking trend of delayed parenthood in developed countries, likely a result of socioeconomic pressures and increasing divorce rates with subsequent remarriage. Increased interest in the "paternal age effect" has driven some private tissue banks to promote cryopreservation of sperm at a young age to avoid the detrimental impacts of aging. Taken together, there is a great need for further investigation into this phenomenon. Although there is solid epidemiological evidence to substantiate the impacts of advanced paternal age on the offspring, the etiological mechanisms that drive this process remain poorly defined. Among the most plausible contributing factors to the increased incidence of various diseases in the offspring of older fathers are age-associated alterations to the sperm epigenome. Specifically, sperm DNA methylation perturbations may have the capacity to affect offspring phenotype through transcription inhibition/activation but have yet to be explored in the context of advancing age. To investigate age-associated sperm DNA methylation alterations, we have analyzed sperm from 17 donors who collected samples between 9 and 19 years apart. DNA methylation was analyzed in all samples at both the global and cytosine phosphate guanine (CpG) level. The results indicate that global sperm DNA methylation increases with age while regional alterations are strongly biased toward hypomethylation, a finding in stark contrast to somatic cell age-associated methylation alterations. Intriguingly, many of the genes affected by regional methylation alteration have been previously suggested to be associated with many types of neuropsychiatric disorders, including schizophrenia, bipolar disorder, developmental delay, personality disorders, and autism. These data provide the first direct evidence that age-associated epigenetic alterations to the sperm represent a plausible mechanism for the increased incidence of various abnormalities in offspring of older fathers.
Type Text
Publisher University of Utah
Subject MESH Paternal Age; Spermatozoa; DNA Methylation; Epigenesis, Genetic; Fathers; Cryopreservation; Disease Susceptibility; Spermatogenesis; Sequence Analysis, DNA; Bipolar Disorder; Schizophrenia; Epigenomics
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of Age-Associated Alternations to Sperm DNA Methylation and Possible Consequences on the Offspring. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Timothy Gerald Jenkins 2013
Format Medium application/pdf
Format Extent 4,253,510 bytes
Source Original in Marriott Library Special Collections. QH9.7 2013.J46
ARK ark:/87278/s6n3354f
Setname ir_etd
Date Created 2014-07-21
Date Modified 2021-05-06
ID 196641
Reference URL https://collections.lib.utah.edu/ark:/87278/s6n3354f
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