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Unlocking the Potential to Treat Male Infertility Through Protein Discovery in Spermatogenesis

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Spermatozoa have a streamlined structure that allows them to move more smoothly through the female reproductive tract to fertilize eggs. However, little is known about this process.

And in a new study published in the Proceedings of the National Academy of Sciences, Japanese researchers have shed new light on a key protein involved in this process.

A team from Osaka University has identified the role of a protein called testicular-specific serine kinase substrate (TSKS) in spermatogenesis, or the release of mature sperm.

During reproduction, sperm must pass through the female reproductive tract to reach the egg in order for fertilization to occur.

To better facilitate this process, spermatogonia have a “streamlined morphology”, which is achieved by removing the cytoplasm (site of many biochemical reactions) of spermatogonia.

Although this process has been observed in previous studies, the underlying molecular mechanisms remain poorly understood.

To understand this process, a research team at Osaka University conducted experiments in mouse models to study the TSKS protein, which is located in membraneless structures called nuage.

“Using genome editing technology, we developed a mouse model in which TSKS was inactivated,” says study co-author Keisuke Shimada. “We found that the spermatozoa of mice with TSKS do not become streamlined, which leads to male infertility.”

TSKS researchers analyzed the sperm of mice and found that these sperm are unable to produce two specific types of nuage called reticulocytes (RB) and chromatid body remnants (CR). Without this nuance, TSKS ruptured spermatogonia cannot properly remove cytoplasm.

In addition, the researchers noticed that the presence of excess residual cytoplasm leads to programmed cell death or apoptosis of these spermatozoa.

“Our results show that the formation of nuage RB and nuage CR is dependent on the TSKS protein. TSKS is required for spermatogonia to clear the cytoplasm and adapt to a streamlined, tadpole-like shape. This applies to humans as well, as the TSKS protein is also present in human semen,” says co-author Sojin Park.

This discovery of the role of TSKS in streamlined spermatogenesis provides further evidence for a single mechanism underlying male infertility. The results of this study can be used in the development of diagnostic tests and male contraceptives.

Source: Medical News.

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