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Durham and Osaka University scientists have discovered a gene that makes mice sperm bind better to an egg. The discovery of the gene, that is essential to mammal fertilisation, makes a protein called PDILT which is thought could help develop fertility treatments in humans.
Image by: xandert, USA
The team found that when the gene was 'switched off' in male mice, less than 3% of eggs were fertilised compared with 80% when the gene was left on. During the study the researchers also found that cumulus cells, which cluster around eggs to protect them, play an important role in reproduction by enabling sperm to bind to an egg.
The discoveries could pave the way for the development of new fertility treatments for humans and improve the effectiveness of in vitro fertilisation (IVF). Ironically, the study could also assist research into new contraceptive techniques that deactivate the gene and prevent sperm from reaching an egg and binding to it.
So how does it work? Dr Adam Benham, School of Biological and Biomedical Sciences, Durham University, said: "The protein is an essential part of the navigation system of sperm. It helps sperm swim through the oviduct to the egg and without it sperm get stuck. Our results show that navigating the oviduct is an important part of the fertilisation process.
The Durham and Osaka study is the first of its kind to discover a gene of this type and then link it to fertility. Dr Bentham likened the process to a kind of sperm navigation system. He said: “You have to programme where it is that you want to go and this protein plays an essential role in getting sperm to the right destination, in good shape, and in good time."
The research at Durham University is funded by the Research Institute for Microbial Diseases, Osaka University in Japan. Dr Masahito Ikawa from Osaka added: "This protein is essential for sperm to migrate successfully and is required for fertility. The next step is to see how this protein works with other proteins to control the sperm binding and fusion process."
Although the research and findings are at an early stage, the researchers now hope to look at how the gene affects sperm-to-egg binding in humans. The full findings are published in the journal Proceedings of the National Academy of Sciences.
Read more anout PDILT and human reproduction
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The researchers found the gene a few years ago through a database search for new genes of the PDI family. Following extensive research, they established that the gene made an important protein in the testes.
The PDILT gene, part of the PDI family, helps another gene product called ADAM3 to form and assemble correctly, and then to reach the surface of a sperm, thereby equipping it with the right tools and machinery to navigate and make contact with an egg.
The new findings show the importance of PDILT in the process of sperm-to-egg binding and in enabling sperm to swim past the uterus, ascend the oviduct and to get through the sticky outer layers of an egg.
The team honed in on the role of the protein by switching it off in mice and tracking the ability of sperm to bind to and fertilise eggs in Petri dishes and in mice. They noticed that sperm from mice with the gene switched off will not bind to a bare egg, but will bind to an egg surrounded by cumulous cells.
Dr Benham said: "We now hope to discover how the PDILT protein affects fertility in humans. Mutations in the gene may be responsible for unexplained male fertility problems and further research may aid more effective IVF treatment."