Researchers say that the sperm wining the race to the egg often effectively poisons its competitors on the way. File Photo by Sebastian Kaulitzki/Shutterstock
Feb. 4 (UPI) -- It turns out that the sperm that win the race to the egg use variants of genetic factors, called distorters, to poison their competitors, according to new research.
Experiments with mouse models suggest a genetic factor called "t-haplotype" is essential to the production of progressive sperm -- the ones capable of winning the race
T-haplotype genes regulate the synthesis of a molecule called RAC1, and the experiments -- detailed Thursday in the journal PLOS Genetics -- showed progressive sperm motility requires just the right amount of RAC1.
"An optimal level of RAC1 is crucial for the capability of individual sperm to swim progressively and thus to reach the oocyte first," study author Alexandra Amaral, scientist at the Max Planck Institute for Molecular Genetics in Berlin, told UPI in an email.
For the study, researchers began by testing the distribution of t-haplotype sperm in different mouse models.
Researchers found sperm motility was greatest in mice featuring an even distribution of t-haplotype sperm and normal sperm, or sperm without the t-haplotype genetic factor.
Mice with only normal sperm featured less progressive motility, while mice with only t-haplotype sperm were sterile.
When scientists observed t-haplotype sperm and normal sperm swimming together, they found t-haplotype were able to swim directly toward the egg, while normal sperm were slow and directionless.
Further analysis revealed levels of RAC1 activity corresponded with the distribution of t-haplotype sperm.
In the sterile mice, where all sperm carried the t-haplotype genetic factor, RAC1 activity was elevated. In mice with only normal sperm, RAC1 levels were low. In mice with the most progressive sperm, RAC1 activity was moderate.
Through a combination of genetic mapping and functional analysis, researchers realized that genetic factors controlling RAC1 activity are expressed when sperm are developing.
In other words, these factors are granted to all sperm.
Because too much RAC1 expression curbs sperm motility, researchers realized something was working to curb RAC1 activity. Excessive RAC1 works like a poison, the scientists concluded, but some sperm were managing to counteract the poison.
"The antidote, called the responder, was also genetically identified and isolated. It turned out to be a dominant-negative form of a protein kinase," said study co-author Bernhard Herrmann.
"It is expressed very late during the haploid phase of spermatogenesis and is not shared between sperm. The antidote rescues sperm that express it, and that are exclusively sperm that contain the t-haplotype," said Herrmann, director at MPIMG and a researcher at the Institute of Medical Genetics and Human Genetics in Berlin.
When researchers treated mixed sperm populations with a substance that inhibits RAC1 activity, they found normal, non-t-haplotype sperm were suddenly able to swim progressively, too, making a b-line for the egg.
Researchers suspect t-haplotype sperm evolved independently in an isolated population of mice, but perhaps with the help of human activity, broke out of isolation and spread quickly across other mice populations.
"In analogy, it is similar to the coronavirus, that evolved in bats without harming them, but once it crossed a species boundary and infected a human being it is now able to spread quickly throughout the world," Amaral said.
Amaral and Herrmann are preparing to test the effects of RAC1 activity on human sperm motility. The researchers suspect the molecule's expression will have a similar impact on the ability of human sperm to swim progressively.
"[If so], then one needs to investigate if sperm from some men having problems to conceive show unbalanced levels of active RAC1," Herrmann said.
"Then we would need to find ways of counterbalancing this. Since RAC1 transmits signals from outside the cell, this can theoretically be done by simply adjusting the sperm culture medium," Herrmann said.