The sperm epigenome and potential implications for the developing embryo
Open accessAbstract
Recent work in the field of male fertility has yielded significant increases in our understanding of the sperm epigenome and its potential role in embryonic development. These new findings have enabled a broad classification of a normal epigenetic state in the male gamete and have provided insight into the possible etiologies of some idiopathic male infertility cases. Histone retention and modification, protamine incorporation into the chromatin, DNA methylation, and spermatozoal RNA transcripts appear to play important roles in the epigenetic state of mature sperm. These epigenetic factors may reveal a historical record of spermatogenesis, portend future functions in embryogenesis, and help to elucidate mechanism of pluripotency. In contrast to the once held dogma regarding the importance of the paternal epigenome, the unique epigenetic landscape in sperm appears to serve more than the gamete itself and is likely influential in the developing embryo. In fact, growing evidence suggests that mature sperm provide appropriate epigenetic marks that drive specific genes toward activation and contribute to the pluripotent state of the embryonic cells. Although not definitive, the current literature provides evidence for the role of the sperm epigenome in the embryo. Future work must be focused on the characterization of epigenetic abnormalities commonly found in individuals with compromised fertility to further establish this role. Additionally, studies should target the effects of environment and aging on the sperm epigenetic program and subsequent fertility loss to determine the etiology of aberrant epigenetic profiles.
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Among epigenetic mechanisms implicated in paternal transmission of stress effects via sperm are DNA methylation, oxidative damage to sperm DNA, histone modifications, and changes in small noncoding RNA including microRNA.
“Among the epigenetic mechanisms that have been implicated in paternal transmission of stress effects via sperm are DNA methylation, oxidative damage to sperm DNA, histone modifications, and changes in small noncoding RNA [175][176][177][178][179] , including microRNA 180,181”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [180]
The Introduction discusses sperm DNA methylation, histone modifications, and RNA transcripts as aspects of the paternal epigenome that may influence embryonic development. The Conclusions and future directions section discusses environmental effects on sperm epigenetics, but does not establish paternal transmission of stress effects or identify oxidative sperm-DNA damage as a mechanism. The sentence cites other sources specifically for microRNA, so that detail is not assessed against this paper. (LLM, conf=0.85)
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Leiser, C. L., Hanson, H. A., Sawyer, K., Steenblik, J., Al-Dulaimi, R., Madsen, T., Gibbins, K., Hotaling, J. M., Ibrahim, Y. O., VanDerslice, J. A., et al. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.10.028 · Cited by 74 · see citing works
Paternal adverse childhood experiences: Associations with infant DNA methylation
Merrill, S. M., Moore, S. R., Gladish, N., Giesbrecht, G. F., Dewey, D., Konwar, C., MacIssac, J. L., Kobor, M. S., & Letourneau, N. L. (2021) · Developmental Psychobiology · doi:10.1002/dev.22174 · Cited by 42 · see citing works
Cannizzaro, E., Ramaci, T., Cirrincione, L., & Plescia, F. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16204031 · Cited by 39 · see citing works
- Authors
- Jenkins, T. G., & Carrell, D. T.
- Affiliations
- University of Utah (US)
- Venue
- Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-06-01
- Volume
- 143
- Issue
- 6
- Pages
- 727-734
- ISSN
- 1470-1626 (ISSN-L)
- 1741-7899
- OpenAlex
- W2129497042
- Cited by
- 232
- References
- 93
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 12 · 2023: 11 · 2022: 6 · 2021: 21 · 2020: 13 · 2019: 19 · 2018: 21 · 2017: 18 · 2016: 14 · 2015: 24 · 2014: 23 · 2013: 29 · 2012: 5
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- sperm epigenome, male fertility, male infertility, histone modifications, histone retention, DNA methylation, embryonic development, pluripotency, paternal epigenetic inheritance, spermatogenesis
- MeSH terms
- Animals, Histones, Humans, Male, Models, Biological, Protein Processing, Post-Translational, Spermatogenesis, Spermatozoa, DNA Methylation, Epigenesis, Genetic, Embryonic Development
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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