Researchers trying to understand what happens in the first moments after fertilisation have discovered that an enzyme previously studied in colon cancer plays a key role.
The study, published in Cell, shows that the enzyme SRPK1 is responsible for unpacking the genetic material stored in the sperm head, once the sperm has fused with the egg. This is the first step in the reorganisation and activation of the paternal genome, which is necessary for the formation of the new embryonic genome.
Co-author Xiang-Dong Fu, Professor of Cellular and Molecular Medicine at University of California, San Diego (UCSD), said: 'We've uncovered a step that might malfunction for some people, and contribute to a couple's difficulty conceiving. Now that we know SRPK1 plays a role here, its potential part in infertility can be further explored'.
DNA is normally tightly coiled around histone proteins to compact the genome and ensure that it can fit within the cell nucleus. Sperm cells are significantly smaller than typical human cells, so a specialised packaging process is required to fit the paternal genome within the sperm nucleus.
During spermatogenesis, the usual DNA packaging histones are replaced by a different protein, protamine, for greater DNA compaction. This process needs to be reversed after fertilisation to ensure that the paternal genome can be reorganised and reprogrammed, ready to interact with the maternal genome.
Professor Fu's research team demonstrated that SRPK1 is responsible for triggering the exchange of protamines for histones after fertilisation, unpacking the paternal genome in preparation for reorganisation and activation. The researchers also noted that SRPK1 played a role in synchronising the remodelling of the paternal genome with that of the maternal genome.
The research team are now conducting further studies to understand how the paternal genome communicates with the maternal genome once fertilisation has occurred. Professor Fu stated, 'the better we understand every step in the process of spermatogenesis, fertilisation and embryogenesis, the more likely we are to be able to intervene when systems malfunction for couples struggling with reproductive issues’.
SRPK1 is also known to play a role in RNA splicing, which regulates protein production within the cell, and has been linked to the development of colon cancer when expressed at abnormally high levels. However, Professor Fu believes that SRPK1 initially evolved to co-ordinate the fertilisation process and subsequently diversified to splice RNA.