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Lack of Prss50 genes severely affects male fertility in mouse model

18 October 2021
Appeared in BioNews 1117

gene previously unknown to have a role in fertility has been found to be essential for healthy sperm.

Researchers from Baylor College of Medicine, Houston, Texas removed both copies of a gene called Prss50, which encodes an enzyme called Protease Prss50. Although the mice did produce sperm, the sperm had abnormal morphology, including bent, multiple, or missing tails. The male mice lacking both copies of Prss50 were severely subfertile.

'The sperm tail is important for fertility because it propels the sperm in its journey to fertilise the egg' explained corresponding author Dr Carolina Jorgez.

During the process of healthy sperm development, certain genes are switched on and off periodically, allowing the sperm to mature. However, in mice lacking the Prss50 genes, this process appears to be disrupted. Instead, the early-development genes that should be switched off, have been incorrectly turned on.

Publishing their findings in the journal Development, Dr Jorgez stated that 'the untimely activation of those genes is disrupting normal sperm development'.

As well as being important for sperm development in mice, Prss50 was found to be highly active in human testes too, suggesting Prss50 may have a role in human fertility.

In humans, infertility can affect approximately one in ten men. Of the men Dr Jorgez and her team studied, around 5 percent had dysfunctional Prss50 genes. Men with two dysfunctional copies of the Prss50 gene were infertile. Conversely, men that have one functional copy of Prss50 were fertile.

Previous studies have often focused on the sperm head's role in infertility, not the tail. In the mice lacking Prss50, the sperm heads were generally unaffected. Notably however, the authors did find a very rare type of abnormal sperm occurring in 1 percent of cases; a head attached to either end of a single tail. This type of sperm abnormality has not been seen in humans, but the authors do not discount that this could exist.

The authors envisage that understanding the genes responsible for healthy sperm will help with diagnosis and informing treatment. 'Our findings are a step towards identifying a panel of genes to screen for male infertility' said Dr Jorgez.

Loss of gene Prss50 results in abnormal sperm tail development and infertility
Baylor College of Medicine |  12 October 2021
PRSS50 is a testis protease responsible for proper sperm tail formation and function
Development |  16 April 2021
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