Some sperm poison their competitors

The competition between sperm cells is fierce – everyone wants to reach the egg cell first to fertilize it. A research team from Berlin now shows in mice that the ability of sperm to move gradually depends on the protein RAC1. Optimal amounts of active proteins improve the competitiveness of individual sperm, while aberrant activity can cause male infertility.

It is literally a race for life when millions of sperm swim to the ova to fertilize it. But pure luck decides which sperm succeeds? As it turns out, there are differences in competitiveness between individual sperm. In mice, a “selfish” and naturally occurring DNA segment breaks the standard rules of genetic inheritance – and assigns a success rate of up to 99 percent to sperm cells that contain it.

A team of researchers from the Max Planck Institute for Molecular Genetics in Berlin describes how the genetic factor called ‘t-haplotype’ promotes the fertilization success of sperm it carries.

The researchers showed for the first time experimentally that sperm with the t-haplotype are more progressive, ie move faster forward than their “normal” counterparts, thus establishing their advantage in fertilization. The researchers analyzed the individual sperm and revealed that most cells that made little progress were genetically ‘normal’, while straight-moving sperm mostly contained the t-haplotype.

Most importantly, they linked the differences in motility to the molecule RAC1. This molecular switch sends signals from outside the cell to the inside by activating other proteins. It is known that the molecule is involved in sending e.g. White blood cells or cancer cells to cells that emit chemical signals. The new data suggest that RAC1 may also play a role in the direction of sperm cells to the egg and a ‘sniff’ towards their target.

“Individual sperm competitiveness appears to depend on an optimal level of active RAC1; either reduced or excessive RAC1 activity impedes effective forward movement,” said Alexandra Amaral, a scientist at MPIMG and first author of the study.

t-sperm poisons their competitors

“Sperm with the t-haplotype succeeds in eliminating sperm without it,” says Bernhard Herrmann, director of the MPIMG and of the Institute of Medical Genetics at Charité – Universitätsmedizin Berlin, and corresponding author of the study. ‘The trick is that the t? ‘Haplotype’ poisons’ all sperm, but at the same time produces an antidote that only works in t-sperm and protects it, ” explains the scientist. “Imagine a marathon in which all participants get poisoned drinking water, but some runners also take an antidote.”

As he and his colleagues found out, the t-haplotype contains certain gene variants that distort regulatory signals. These distorting factors are detected in the early stages of spermatogenesis and spread among all sperms of a mouse with the t-haplotype. These factors are the ‘poison’ that disturbs progressive movement.

The ‘antidote’ takes effect after the collection of chromosomes is evenly distributed among the sperm during ripening – each sperm cell now contains only half of the chromosomes. Only half of the sperm with the t-haplotype yields an additional factor that reverses the negative effect of the distortion factors. And this protective factor is not distributed but retained in t-sperm.

t-sperm have no benefit when they are alone

In sperm from male mice with the t-haplotype only on one of their two chromosomes 17, the researchers observed that some cells move forward and that some make little progress. They tested some sperm and found that the genetically ‘normal’ sperm are the ones that usually do not move straight. When they treated the mixed population of sperm with a drug that inhibits RAC1, they noticed that genetically ‘normal’ sperm could now also swim progressively. The benefit of t-sperm is gone, showing that aberrant RAC1 activity impedes progressive motility.

The results explain why male 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, as the researchers have now found, and are almost immobile.

But sperm from normal mice treated with the RAC1 inhibitor also lose their ability to move progressively. Too low a RAC1 activity is therefore also detrimental. Abnormal RAC1 activity may also underlie certain forms of male infertility in men, the researchers speculate.

“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,” says the scientist.