Sperm use poison to disable competitors

A genetic factor helps some sperm outcompete others to reach the egg cell first.

Researchers from the Max Planck Institute for Molecular Genetics in Berlin, Germany have discovered that the protein RAC1, which plays a role in the movement of cells, controls the motility and competitiveness of sperm cells in mice.

'The competitiveness of individual sperm seems to depend on an optimal level of active RAC1; both reduced or excessive RAC1 activity interferes with effective forward movement,' said Dr Alexandra Amaral, first author of the study.

Classical Mendelian genetics predicts that sperm cells have an equal chance in the 'fertilisation race'; however, the t-haplotype is a genetic variant that breaks these rules of inheritance by increasing the fertilisation success rate of sperm cells that carry it.

The results of the study, published in PLOS Genetics, show that sperm from mice carrying the t-haplotype variant swam faster and in straight lines directly towards the egg cell, whereas the movement of normal sperm cells without the variant was directionless and slow.

The scientists discovered that the differences in motility were due to the levels of RAC1. RAC1 activity was elevated in sterile mice, where all the sperm cells carry the t-haplotype variant, while RAC1 levels were low in mice that only carry normal sperm cells. In mice that produce a mixture of normal and t-haplotype sperm cells they observed that some sperm cells showed progressive movement and others were less progressive. They reported that it was the normal sperm cells that made little progress. They then treated this mixed population of sperm cells with a compound that inhibits RAC1 activity and showed that this enabled the normal sperm cells to swim progressively.

The team also found that the t-haplotype variant contains certain genetic factors called distorters that inhibit the progressive movement of sperm cells by interfering with the cell signalling molecules required for motility.

'Sperm with the t-haplotype manage to disable sperm without it. The trick is that the t‑haplotype 'poisons' all sperm, but at the same time produces an antidote, which acts only in t-sperm and protects them, ' said Professor Bernhard Herrmann, director of the Department of Developmental Genetics at the Max Planck Institute for Molecular Genetics and corresponding author of this study.

The researchers suggest that abnormal RAC1 activity may underlie certain forms of infertility in men and they are planning to investigate the effect of RAC1 activity on the motility of human sperm.

'Sperm immotility is a big deal in male infertility. Investigating the levels of this protein in human samples could help to develop treatments for infertility in men,' said Professor Herrmann.