Sperm Cells Poison Competitors, Those with Optimal Mobility Controlling Protein Wins the Race to the Egg

Fertilization of an egg is a fierce competition between millions of sperm cells, a frantic race to reach the egg cell first. While Mendelian genetics suggests that all the sperm cells in the race are identical and have equal chances of fertilizing the egg, a new study in PLoS Genetics reports that all sperm cells are not made equal. Some are more capable than others with the advantage of better mobility and speed.

Research Model System

t-haplotype is a naturally occurring genetic variant in mice on chromosome 17, which encodes several genes and does not follow Mendelian inheritance laws. The t-haplotype dominates the wildtype in that 99% of offspring of a heterozygous t/+ male will inherit the t-haplotype variant.

Various studies have shown that this dominant inheritance is due to the effect the t-haplotype has on sperm motility. Using this model system, scientists from the Max Planck Institute for Developmental Genetics, Berlin, demonstrate that RAC1, a protein from the Rho GTPase family, is involved in controlling the progressive movement of sperm.

Results

The authors of the report found that sperm motility in mice with t-haplotype was better than wildtype mice, and this was due to increased expression of RAC1 in the t-haplotype mice. While the t-haplotype encodes genes such as RAC1, which impair sperm motility and speed, there is a dominant-negative kinase SMOK^TCR, a flagellar motor that enables t-sperm to rescue their mobility.

By studying single sperm cells in t/+, wildtype, and t/t mice, the authors observed that the expression of RAC1 controls the effect of t-haplotype on sperm velocity and motility.

Hence, while t/t mice are sterile due to increased levels of RAC1, which render the sperm immotile; heterozygous t/+ mice can overcome the t-haplotype induced motility defects. The SMOK^TCR rescue acts exclusively on t-sperm, giving them an advantage over normal sperm cells. Interestingly, normal mice when treated with RAC1 inhibitors have low motility sperm, suggesting that there is a precarious balance of RAC1 levels maintained in the sperm for optimal mobility.

This is the first experimental evidence that t-haplotype mouse has sperm that is faster due to progressive movement and hence outperform the sperms with normal genotype to reach the egg faster, suggesting that sperm cells are indiscriminate in their quest to pass on their genes, further underlying selective pressure as a common mode of evolution.

“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,” explained first author, Alexandra Amaral. According to lead author Prof. Bernhard Hermann, “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,” he further explained. “Imagine a marathon, in which all participants get poisoned drinking water, but some runners also take an antidote.”

Related Article: Endometriosis Precision Detection Company, V-CHECK Eyes Global Market

References

1. https://www.mpg.de/16367201/0201-moge-not-all-sperm-are-equal-151795-x?c=2249
2. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009308

Author

Sahana Shankar