Shocking revelation: an electrically-activated protein regulates spermatogenesis

Osaka, Japan – Frankenstein’s monster was brought to life by the judicious application of a little electricity; and a surprising number of processes in our bodies are regulated by electrical currents too. Now, researchers from Japan reveal that electricity just may play a key role in male fertility.

In a study recently published in Nature Communications, researchers from Osaka University have revealed that a protein whose activity is dependent on electrical signals plays a crucial part in sperm development.

Sperm go through a developmental process as they move through the male reproductive system that allows them to mature and acquire the ability to fertilize an egg. Part of this process involves changing the types of lipids, or fatty molecules, that are present in sperm cell membranes. These changes are enacted by enzymes, which have to be activated at a specific point in the sperm development timeline.

“We recently identified the functional expression of an unusual voltage-sensing phosphatase (VSP) in spermatozoa. This unique protein shows phosphatase activity in response to changes in cell membrane potential,” says lead author of the study Takafumi Kawai. “However, it remained unclear whether VSP senses the membrane potential of spermatozoa, and if so, how this affects spermatozoa maturation.”

To explore this, the researchers eliminated VSP expression in mouse sperm. They then evaluated the lipid content of the sperm cell membranes at different stages of sperm development in the cells without VSP compared with cells with VSP.

“The results were very clear,” states Yasushi Okamura, senior author. “In the absence of VSP, the certain membrane lipid composition was not completely matured in spermatozoa, suggesting that VSP is required for proper spermatozoa development.”

Next, the researchers created a mutant version of VSP that changed its responsiveness to electrical stimulation and tested the effects of this mutant in mice. Compared with normal mice, sperm from the mice expressing the mutant protein were noticeably abnormal in motility.

“Our findings show that, in developing sperm, VSP responds to electrical signals by promoting appropriate maturation of the cell membrane,” says Kawai.

Given that proper sperm development and function are crucial to male fertility, the findings from this study could be used to help develop clinical treatments for infertility in the future. In addition, investigating the unique mechanism by which VSP converts electrical signals into chemical signals is likely to provide new insight into cell development.

###
The article, “The Significance of Electrical Signals in Maturing Spermatozoa for Phosphoinositide Regulation Through Voltage-Sensing Phosphatase,” was published in Nature Communications at DOI: https://doi.org/10.1038/s41467-024-51755-2

About Osaka University
Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Website: https://resou.osaka-u.ac.jp/en