BERLIN, Germany – The biological race between sperms to reach an egg is a hard and competitive process. Now, say researchers in Germany, they have discovered which protein gives the sperm the winning advantage. According to their study, a molecular “switch” in sperm can also allow men to turn their fertility on and off.
Experiments on mice find that the ‘winner’ contains a number of toxic mutations that poison competing sperm. According to researchers, a genetic factor called ‘t-haplotype’ promotes the success of the sperm it carries. They are also fueled by a protein called RAC1, the molecular switch that drives sperm forward.
Can the sperm ‘link’ promote or suppress fertility?
Sperm with this protein move faster than their counterparts, creating an advantage in whoever reaches the egg first. The findings are also expected to apply to humans. It can lead to a pill that increases fertility in men, or a male oral contraceptive.
This chemical will target, increase or decrease the levels. Too much, however, can cause male infertility. On average, a man produces 80 to 300 million sperm every time he ejaculates. Nevertheless, more than 60 percent of fertility problems are related to poor sperm, so it is important to keep them healthy.
“Sperm with the t-haplotype succeeds in eliminating sperm without it,” says the corresponding author Bernhard Herrmann of the Max Planck Institute for Molecular Genetics in a university release.
The trick is that the t-haplotype ‘poisons’ all sperm, but at the same time produces an antidote that only works in the t-sperm and protects it. Imagine a marathon in which all participants get poisoned drinking water, but some runners also take an antidote. ”
Scientists find the ‘antidote’ to poorly performing sperm
The study found that some genes contain mutations that distort regulatory signals, which are then spread to all sperm. It is the ‘poison’ that disturbs progressive movement. The ‘antidote’ takes effect after the set of chromosomes is evenly distributed among the sperm during maturation, and each cell now contains only half.
Only those with the t-haplotype yield an additional factor that reverses the negative effect. Optimal amounts of RAC1 improve the competitiveness of individual sperm, and offer new hope in the fight against male infertility.
It is literally a race for life when millions of sperm swim to egg cells to fertilize it. Herrmann and colleagues describe t-haplotype as a “selfish” and naturally occurring DNA segment. It violates the standard rules for genetic inheritance and assigns a success rate of up to 99 percent to sperm cells that contain it.
The analysis of individual sperm showed that most made little progress and were genetically normal. On the other hand, straight moving sperm contains the t-haplotype. Most importantly, RAC1 has been identified as the key to differences in motility. It sends signals from outside the cell to the inside by activating other proteins. RAC1 also directs sperm cells to the egg and sniffs their way to the target.
“The competitiveness of individual sperm appears to depend on an optimal level of active RAC1; both reduced or excessive RAC1 activity impedes effective forward movement, ”adds Alexandra Amaral, the first author.
‘Merciless competitors’
When the researchers treated the mixed population of sperm with a substance that inhibits RAC1, genetically ‘normal’ sperm can now swim progressively. The benefit of t-sperm has disappeared. The results explain why mice with two copies of the t-haplotype, one on each of the two chromosomes 17, are sterile.
They only produce sperm that carry the t-haplotype. These cells have much higher levels of active RAC1 than sperm from genetically normal mice. However, sperm from normal mice treated with the RAC1 inhibitor also lost their ability to move progressively. In other words, too little RAC1 activity is also detrimental. According to the researchers, abnormal RAC1 activity may also be the underlying problem in forms of human infertility among men.
“Our data highlights the fact that sperm cells are relentless competitors,” says Herrmann.
Furthermore, the example of the t-haplotype shows how some genes use somewhat dirty tricks to be passed on.
“Genetic differences can give individual sperm an advantage in the race for life, thus promoting the transmission of specific gene variants to the next generation.”
The groundbreaking study appears in the journal PLoS Genetics.
SWNS author Mark Waghorn contributed to this report.