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Cited by 137Epigenetics and DNA MethylationGenetic Syndromes and ImprintingSperm and Testicular Function

Genetic and Epigenetic Variation, but Not Diet, Shape the Sperm Methylome

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Shea, Jeremy M., Serra, Ryan W., Carone, Benjamin R., Shulha, Hennady P., Kucukural, Alper, Ziller, Michael J., Vallaster, Markus P., Gu, Hongcang +5 more·2015·Developmental Cell
DOI 10.1016/j.devcel.2015.11.024PMC PMC4691283
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Abstract

Paternal diet can impact metabolic phenotypes in offspring, but mechanisms underlying such intergenerational information transfer remain obscure. Here, we interrogate cytosine methylation patterns in sperm obtained from mice consuming one of three diets, generating whole genome methylation maps for four pools of sperm samples and for 12 individual sperm samples, as well as 61 genome-scale methylation maps. We find that "epivariation," either stochastic or due to unknown demographic or environmental factors, was a far stronger contributor to the sperm methylome than was the diet consumed. Variation in cytosine methylation was particularly dramatic over tandem repeat families, including ribosomal DNA (rDNA) repeats, but rDNA methylation was strongly correlated with genetic variation in rDNA copy number and was not influenced by paternal diet. These results identify loci of genetic and epigenetic lability in the mammalian genome but argue against a direct role for sperm cytosine methylation in dietary reprogramming of offspring metabolism.

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  • Studies on transgenerational effects of endocrine disruptors and of high fat diet on the DNA methylome have recently been challenged by others.

    “While most of published studies are technically sound, the majority still await independent confirmation; studies on transgenerational effects of endocrine disruptors and of high fat diet on the DNA methylome have recently been challenged by others10,11.”

    From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [11]

    The Discussion (page unavailable) reports no consistent effect of high-fat diet on the mouse sperm methylome, supporting the claim that dietary methylation effects have been challenged. Our copy does not address endocrine disruptors, and the Results caution that differences in strain and regimen mean its findings do not necessarily dispute a prior dietary report. (LLM, conf=0.88)

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Authors
Shea, J. M., Serra, R. W., Carone, B. R., Shulha, H. P., Kucukural, A., Ziller, M. J., Vallaster, M. P., Gu, H., Tapper, A. R., Gardner, P. D., Meissner, A., Garber, M., & Rando, O. J.
Affiliations
  • University of Massachusetts Chan Medical School (US)
  • Broad Institute (US)
Corresponding author
Rando, Oliver J.
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2015-12
Volume
35
Issue
6
Pages
750-758
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2015.11.024
PMC
PMC4691283
OpenAlex
W2217449599
Cited by
137
References
2
Citations by year
2026: 2 · 2025: 7 · 2024: 5 · 2023: 12 · 2022: 5 · 2021: 11 · 2020: 12 · 2019: 24 · 2018: 30 · 2017: 11 · 2016: 17 · 2015: 1
FWCI
8.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • National Institutes of Health (UL1TR001453, UL1TR000161)
  • National Institute on Drug Abuse (R01DA033664, R01DA036898, F32DA034414)
  • National Institute of Environmental Health Sciences (DP1ES025458)
  • National Center for Advancing Translational Sciences
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD080224, R01HD078679, T32HD007439)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
sperm methylome, cytosine methylation, paternal diet, intergenerational epigenetic inheritance, ribosomal DNA repeats, rDNA copy number, tandem repeats, genome-wide methylation mapping
MeSH terms
Animals, Diet, DNA, Ribosomal, Male, Spermatozoa, Genetic Variation, Genome, DNA Methylation, Epigenesis, Genetic, Mice, Epigenomics

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