Researchers from the University of Osaka, Japan, have identified two specific proteins essential for proper sperm function and movement.
The findings could pave the way for new diagnostic tools and treatments for couples struggling to conceive.
The study focused on the sperm’s flagellum, or tail, a whip-like structure whose motion propels the sperm forward.
Sperm that can’t swim well have a much lower chance of leading to a successful pregnancy.
When the flagellum is malformed or its movement is impaired, the sperm cannot travel efficiently, leading to male infertility.
“The structure of the sperm flagellum is quite complex and includes radial spokes, which are essential for controlling flagellar motion,” said Haoting Wang, lead author of the study, in the press release.
“CFAP91 is a radial spike protein and has been implicated in human male infertility, but it is unclear why it has this effect,” Wang added.
Protein role in sperm development
Inside every flagellum is an incredibly complex structure, including tiny components called radial spokes. These are essential for controlling the whip-like motion that propels sperm forward.
CFAP91 is one of the proteins in these radial spokes, and it has a known connection to male infertility in humans.
To investigate the function of the protein CFAP91 in sperm development, researchers created “knockout” mice that were genetically modified not to produce this protein.
The sperm of these mice was examined, paying close attention to their shape and how they moved.
Furthermore, the team reintroduced the protein into the same mice to understand what CFAP91 interacts with.
They also used a technique called proximity labeling on mature sperm to pinpoint other proteins located near CFAP91, thereby building a more complete picture of its molecular network.
“The results were very clear. Cfap91 knockout mice not only exhibited impaired sperm flagellum formation, but also had male infertility,” noted Haruhiko Miyata, senior author.
By reintroducing CFAP91 and using advanced techniques, the researchers identified its role and the proteins it interacts with.
It was found that CFAP91 acts as a scaffold, a key component for assembling the radial spoke 3 (RS3) complex in the flagellum. The entire structure is compromised without this scaffolding protein, leading to the observed defects.
Sperm movement
In a second key discovery, the study used a technique called proximity labeling to identify another protein, EFCAB5, which is located near CFAP91 in mature sperm.
The researchers demonstrated that EFCAB5 serves as a “sperm-specialized movement regulator,” and when it’s absent, male fertility is reduced.
“Our findings show that CFAP91 affects male fertility because it serves as a scaffold for assembling the radial spokes. In addition, we showed that the nearby protein EFCAB5 is crucial for controlling specialized sperm movement,” Wang concluded in the press release.
Infertility can be difficult to diagnose due to its many possible causes.
The findings from this study add to it, shedding light on the structure of sperm and its role in male fertility.
The insight into how particular sperm proteins work may lead to the creation of new tools for diagnosing and treating male infertility.