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Analysing the sperm epigenome: roles in early embryogenesis and assisted reproduction

Abstract

An understanding of the epigenetic mechanisms involved in sperm production and their impact on the differentiating embryo is essential if we are to optimize fertilization and assisted reproduction techniques in the future. Male germ cells are unique in terms of size, robustness, and chromatin structure, which is highly condensed owing to the replacement of most histones by protamines. Analysis of sperm epigenetics requires specific techniques that enable the isolation of high quality chromatin and associated nucleic acids. Histone modification, DNA methylation and noncoding RNAs have important, but so far underestimated, roles in the production of fertile sperm. Aberrations in these epigenetic processes have detrimental consequences for both early embryo development and assisted reproductive technology. Emerging computational techniques are likely to improve our understanding of chromatin dynamics in the future.

Key Points

  • During human spermatogenesis, most histones are replaced by protamines resulting in chromatin condensation and inactivation of transcription

  • Although sperm is a transcriptionally inactive cell, the remaining histones are highly acetylated and are not randomly distributed throughout the genome

  • The specific constitution of sperm cells (robust stable surface, small size, unique chromatin structure) requires appropriate techniques for analysis of epigenetics

  • Increasing evidence suggests that sperm epigenetics have a critical role in fertile sperm production, embryo development and assisted reproduction

  • Sperm are commonly accepted to have two epigenetic programs, one reflecting the epigenetic events of spermatogenesis and the other representing epigenetic events required for embryo development

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Figure 1: Overview of sperm epigenetics.
Figure 2: Analysis of DNA methylation in sperm.
Figure 3: Analysis of DNA–histone interaction in sperm.
Figure 4: Sperm miRNA analysis.

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Acknowledgements

The authors wish to acknowledge grant support from the German Research Foundation (DFG), Clinical Research Unit KFO 181, projects 1 (STE 892/9-2) and 6 (SCHA 1531/1-1).

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Schagdarsurengin, U., Paradowska, A. & Steger, K. Analysing the sperm epigenome: roles in early embryogenesis and assisted reproduction. Nat Rev Urol 9, 609–619 (2012). https://doi.org/10.1038/nrurol.2012.183

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