In pioneering research that can help explain infertility cases of unknown cause, researchers at the University of California-San Diego's School of Medicine have discovered that an enzyme called 'SPRK1' leads the first step in untangling a sperm's genome, kicking out special packing proteins, which opens up the paternal DNA and allows for merging with mother's DNA -- all in a matter of hours.
To date, researchers did not really know much about these relatively brief, yet crucial, incipient moments in fertilisation. "In this study, we were simply interested in answering a fundamental question about the beginning of life," said senior author Xiang-Dong Fu.
"But in the process, we've uncovered a step that might malfunction for some people, and contribute to a couple's difficulty conceiving. Now that we know SPRK1 plays a role here, its potential part in infertility can be further explored,' he added in a paper published in the journal Cell.
The genetic material in the sperm
While sperms carry only half as much genetic material as a regular cell, it needs to be folded and packaged in a special way in order to fit. One way nature does this is by replacing histones -- proteins around which DNA is wound, like beads on a necklace -- with a different type of protein called protamines. Fu's team has long studied aSPRK1' for a completely different reason: its ability to splice RNA, an important step that enables the translation of genes to proteins.
They previously showed that SPRK1 is over-activated in colon cancer, and they developed inhibitors to dampen the enzyme. According to Fu, SPRK1 most likely started out playing this role in early embryogenesis, then later evolved the ability to splice RNA. In this way, SPRK1 gets to stick around even when it's no longer needed for embryogenesis.
Fu and his team want to determine the signals that instruct sperm to synchronize with the maternal genome. "We have a ton of new ideas now," Fu said. "The better we understand every step in the process of spermatogenesis, fertilization and embryogenesis, the more likely we are to be able to intervene when systems malfunction for couples struggling with reproductive issues."
