Gene involved in sperm-to-egg binding is key to fertility in mammals

May 1, 2012, Durham University

Experts from Durham University have identified a new gene that could help the development of fertility treatments in humans in the future.

Scientists from Durham University, UK, and Osaka University, Japan, looking at fertility in mice, have discovered for the first time that the gene, which makes a protein called PDILT, enables to bind to an egg, a process essential to fertilisation.

The team found that when the gene was 'switched off' in male mice, less than three per cent of females' eggs were fertilised compared to more than 80 per cent in mice when the gene was left switched on.

It is the first time that a gene of this type has been linked to fertility.

The researchers also found that the , a cluster of cells surrounding and protecting an egg, play an important role in fertility - their presence enables sperm to bind properly to an egg.

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 findings are published in the journal PNAS, Proceedings of the National Academy of Sciences.

Sperm from normal male mice bind to female eggs, but sperm from the males lacking PDILT cannot bind to the egg. Credit: Masahito Ikawa, Osaka University and PNAS

The discoveries could pave the way for the development of new fertility treatments for humans that could help to reduce the cost and improve the effectiveness of in vitro fertilisation (IVF). They could also assist research into new contraceptive techniques that deactivate the gene and prevent sperm reaching an egg and binding to it.

Dr Adam Benham, School of Biological and , 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.

"Like any navigation system, 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 researchers found the gene a few years ago through a database search for new 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."

Dr Masahito Ikawa from Osaka University, Japan, added: "This protein is essential for sperm to migrate successfully and is required for fertility. The next step is to see how this works with other proteins to control the sperm binding and fusion process."

More information: PNAS March 6, 2012 vol. 109 doi: 10.1073/pnas.1117963109

Related Stories

Recommended for you

Blood-vessel-on-a-chip provides insight into new anti-inflammatory drug candidate

January 15, 2018
One of the most important and fraught processes in the human body is inflammation. Inflammatory responses to injury or disease are crucial for recruiting the immune system to help the body heal, but inflammation can also ...

Molecule produced by fat cells reduces obesity and diabetes in mice

January 15, 2018
UC San Francisco researchers have discovered a new biological pathway in fat cells that could explain why some people with obesity are at high risk for metabolic diseases such as type 2 diabetes. The new findings—demonstrated ...

Obese fat becomes inflamed and scarred, which may make weight loss harder

January 12, 2018
The fat of obese people becomes distressed, scarred and inflamed, which can make weight loss more difficult, research at the University of Exeter has found.

Optimized human peptide found to be an effective antibacterial agent

January 11, 2018
A team of researchers in the Netherlands has developed an effective antibacterial ointment based on an optimized human peptide. In their paper published in the journal Science Translational Medicine, the group describes developing ...

Research discovers possible link between Crohn's and Parkinson's in Jewish population

January 11, 2018
Mount Sinai Researchers have just discovered that patients in the Ashkenazi Jewish population with Crohn's disease (a chronic inflammatory of the digestive system) are more likely to carry the LRRK2 gene mutation. This gene ...

Scientists use gene expression to understand how astrocytes change with age

January 11, 2018
Potentially explaining why even healthy brains don't function well with age, Salk researchers have discovered that genes that are switched on early in brain development to sever connections between neurons as the brain fine-tunes, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.