Gene essential for producing functional sperm explored

Disruption to a gene causes malformations to the development of sperm tails, resulting in mice producing no functional sperm.

A gene has been identified as having a key role in the production of healthy sperm cells, opening a potential avenue into understanding male infertility. A combined Japanese–German research team removed POC5, a key protein in the formation of a scaffold at the base of sperm tails, by knocking out its corresponding gene in male mice. The resulting scaffolds were improperly developed in the knockout mice, resulting in sperm with poorly constructed tails.

'While the causes of female infertility have been studied extensively, the mechanisms underlying male infertility, which are known to account for about half of all infertility cases, remain poorly understood,' said lead researcher Dr Hiroki Shibuya from the RIKEN Centre for Biosystems Dynamics Research in Kobe, Japan.

In a paper published in Science Advances, the team, in collaboration with Professor Manfred Alsheimer from Julius Maximilians University in Würzburg, Germany, used ultrastructure expansion microscopy to closely examine the structure of mouse germ cells. They focused specifically on the centrioles – a pair of small cylindrical structures that form part of the scaffold at the base of sperm tails.

As they were already aware that POC5 was involved in the scaffold's form and function, the team used CRISPR-based genome editing to knock out the POC5 gene. Despite having no other medical conditions, every knockout mouse in the study was found to be completely infertile, as the lack of properly functioning tails left the sperm unable to travel through the testes. The team also assessed the effect of POC5 on similar structures in somatic cells, such as cilia, concluding that POC5 is not crucial to the assembly of these structures.

'Our modified expansion microscopy protocol can be extended to other analyses, including human sperm, opening new possibilities for investigating fine structural abnormalities that account for male infertility,' said Dr Shibuya. 'In the long term, this could lead to novel diagnostic and therapeutic approaches in reproductive medicine.'

Looking forward, the team are seeking to understand the mechanisms behind these malformations, as well as understanding whether POC5 plays a similar role in sperm development in other species, including humans. With male infertility believed to play a factor in 50 percent of couples affected by infertility worldwide, the researchers hope they can provide greater insight into understanding human infertility.