Protein behind streamlined sperm opens door for male contraceptives

Swimmers in Speedo’s controversial LZR racer suit at the 2008 Beijing Olympics broke 23 out of 25 world records, proving that being more streamlined is an advantage. A new study from Japan has shown that the same theory applies to sperm.

Sperm must pass through the female reproductive tract to fertilize the egg. With hundreds of millions of people competing for the one egg, it’s imperative to stay ahead of the competition. It is the streamlined design of the sperm that allows for rapid movement, thereby providing its benefits.

It is well known that immature spermatozoa (spermocytes) are surrounded by a gelatinous liquid, the cytoplasm. To be more streamlined, mature sperm must discard their cytoplasm before they are released from the Sertoli cells that created them, in a process called spermatogenesis. The process of shedding sperm cell cytoplasm has been observed in previous studies, but the underlying molecular mechanisms remain unclear.

Within germ cells that develop into eggs or sperm are small, RNA-rich, membraneless structures called nuages. Nuage is thought to be essential for germ cell specialization and interacts with testis-specific serine kinase substrates (TSKS), protein-encoding genes involved in sperm production.

Researchers at Osaka University in Japan investigated how deleting the entire coding sequence of mouse TSKS using the CRISPR/Cas9 system affected the shape of sperm produced by mice.

“Using genome-editing technology, we developed a mouse model in which TSKS is disrupted,” said Keisuke Shimada, co-first author of the study. “We found that sperm from mice with disrupted TSKS failed to form a streamlined morphology, resulting in male infertility.”

The researchers found that when TSKS were disrupted, spermatids did not produce two specific types of nuages: reticular bodies (RB) and chromatid remnants (CR). Without RB and CR, mouse sperm cannot properly release the cytoplasm, ultimately leading to cell death (apoptosis). This study indicates that TSKS are essential for the formation of RB and CR nuages.

“Our results showed that the generation of RB and CR nuages ​​is dependent on TSKS,” said Soojin Park, co-lead author of the study. “TSKS are necessary for sperm to clear the cytoplasm and adapt to the streamlined tadpole shape.”

Although this study highlights the link between TSKS and nuage, the molecular mechanisms underlying the cytoplasmic elimination process remain enigmatic and require further study.

“There are many missing links between TSKS function and the process of spermatogenesis, but gaining more knowledge about TSKS and related proteins may help us understand these mechanisms,” said the researchers. increase.

Regardless, the findings of this study are relevant for diagnosing and treating infertility and have the potential to develop male contraceptives.

“Our work can contribute to understanding spermatogenesis, genetic diagnosis of idiopathic male infertility, and treatment of infertile patients,” said the researchers. “[T]His findings could lead to the development of male contraceptives, if compounds that inhibit spermatogenesis can be found. “

The study was published in a journal Proceedings of the National Academy of Sciences.

Source: Osaka University



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