Keywords
1. Age-related DNA methylation
2. Bull sperm epigenetics
3. IVF embryo quality
4. Sperm aging fertility
5. Epigenetic reprogramming
The natural aging process is known to cause various physiological changes in living organisms, but recent research has unveiled the age-associated epigenetic transformations that occur in the sperm of bulls, which might have implications on fertility and the developmental potential of embryos. In a pioneering study published in “The Journal of Reproduction and Development,” researchers explored the dynamics of DNA methylation in bull spermatozoa with aging and how these modifications may translate to early embryonic development post in vitro fertilization (IVF). Led by Dr. Kumiko Takeda and her team from the Institute of Livestock and Grassland Science, NARO, Japan, this study constitutes a significant contribution to understanding fertility and reproduction in livestock, with potential translational applications to human fertility research.
DOI: 10.1262/jrd.2018-146
Introduction to the Study
The comprehensive study revealed changes in DNA methylation levels at specific CpG sites in bull spermatozoa associated with different ages, raising questions about the potential implications of these modifications on fertilization and the early stages of embryonic development. DNA methylations, which involve the addition of a methyl group to the DNA strand at particular cytosine bases, have been illustrated as critical regulators in gene expression and are thus likely to affect seminal and reproductive qualities.
Methodology
The research focused on cryopreserved semen samples from a Japanese Black bull collected at five distinct ages, labeled JD1 through JD5, corresponding to 14, 19, 28, 54, and 162 months, respectively. The team initially utilized genome-wide DNA methylation analysis to trace patterns and then employed Combined Bisulfite Restriction Analysis (COBRA) to confirm age-related methylation differences at nine CpG sites. The subsequent in vitro fertilization results offered insights into the implications of these sperm methylation patterns on embryo development.
Findings
Among the methylated sites scrutinized, eight exhibited increased methylation with age, while one site showed hypomethylation. Most notably, these alterations typically transpired rapidly at younger ages. However, despite these methylation changes in bull spermatozoa, they observed that the derived IVF blastocyst-stage embryos commonly exhibited low methylation levels in specific CpG regions, indicating a fascinating aspect of epigenetic reprogramming following fertilization.
Discussion
The significance of these findings lies in their potential to influence our understanding of age-dependent fertility declines, not only in cattle but possibly extending to other mammalian species, including humans. The epigenetic changes traced in this study could conceivably be related to the decrease in fertility seen with advancing paternal age and could also impact the developmental competence of embryos for livestock industry productivity or even assisted human reproduction technologies.
Future Perspectives
Additional research is warranted to ascertain how these age-dependent methylation changes in sperm DNA might impact the long-term development and health of offspring. Such investigations are crucial given that paternal epigenetics, and especially DNA methylation, is known to influence embryogenesis and could potentially lead to transgenerational health effects.
References
1. Takeda, K., Kobayashi, E., Nishino, K., Imai, A., Adachi, H., Hoshino, Y., … & Watanabe, S. (2019). Age-related changes in DNA methylation levels at CpG sites in bull spermatozoa and in vitro fertilization-derived blastocyst-stage embryos revealed by combined bisulfite restriction analysis. The Journal of Reproduction and Development, 65(4), 305-312. doi: 10.1262/jrd.2018-146
2. Rahman, M.B., Schellander, K., Luceño, N.L., & Van Soom, A. (2018). Heat stress responses in spermatozoa: Mechanisms and consequences for cattle fertility. Theriogenology, 113, 102–112. doi: 10.1016/j.theriogenology.2018.02.007
3. Jenkins, T.G., Carrell, D.T. (2012). Dynamic alterations in the paternal epigenetic landscape following fertilization. Frontiers in Genetics, 3, 143. doi: 10.3389/fgene.2012.00143
4. Kaneda, M., Okano, M., Hata, K., Sado, T., Tsujimoto, N., Li, E., & Sasaki, H. (2004). Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature, 429, 900-903. doi: 10.1038/nature02633
5. Jenkins, T.G., Aston, K.I., Cairns, B.R., Carrell, D.T. (2014). Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genetics, 10(7), e1004458. doi: 10.1371/journal.pgen.1004458
Conclusion
Dr. Kumiko Takeda’s research discloses important age-related methylation changes in bull spermatozoa and the potential impact of these alterations on IVF-derived embryo development. This study calls attention to the importance of epigenetic factors in paternal aging and fertility, stimulating future research in animal breeding, biotechnology, and perhaps, human reproductive medicine. Understanding how such epigenetic modifications can influence fertilization and subsequent embryonic growth is of paramount importance, not just for the breeding success of cattle but also for human health and disease prevention in the context of assisted reproductive technologies.