The first report came from researchers in the US and the Iran. They discovered a gene mutation which might be the trigger for male sterility, the gene Catsper1 which provides for motion during fertilization. If this gene is defect or missing, the ovum cannot be fertilized, a fact already proven in studies with mice. The wrongdoer though was unknown so far. Dr. Michael Hildebrand, PhD, Otolaryngologist at the University of Iowa, and his team set off now to find traces. During a study with Iranian families they collected genetic information on a variety of inheritable disorders such as deafness, kidney insufficiency as well as infertility. Among the test persons happened to be two families with both, fertile and – genetically caused – infertile men. By comparison of their DNA the researchers identified two mutations most likely responsible for the damage respectively the lack of the Catsper1 protein. Neither of those mutations was found within a control group of 576 Iranians. The result of this study was published in the latest American Journal of Human Genetics.
A long way to the pill for men
If additional studies confirm current results, it would be possible to stop fertilization of an ovum with a drug binding to the Catsper1-protein, states the co-leader Hildebrand. But it’s a long road yet to get there. There are no animal experiments to first of all test the efficiency of the pill yet. “It’s clear that those tests will take several years”, confirms Hildebrand. But he assumes that it is possible to develop a safe drug free of side effects, mainly because the protein is found only in sperm cells. He does not see a problem in reversibility as well. Remedying male infertility requires a different approach. “Here we proceed from the assumption of some kind of “gene therapy” explains the researcher. The defect gene will be replaced with a normal Catsper1 protein. This procedure was already tested on animals but is not safe yet to be transferred to humans.
Sperm-gestation process analyzed on a molecular level
Just a little while later, the second pill report followed by researchers at the Rensselaer Polytechnic Institute in Troy. They are also involved in looking for a new approach regarding male conception. Basis here is the fact that sperms go through a gestation process which makes them fertile on their way from the vagina to the ovum. If they succeed to rescind this process, i. e. capacitation, they had the solution for contraception for men says Mark Platt PhD, chemist and specialist in the field of mass spectrometry. With the aid of isotopic labelling, tandem mass spectrometry and chromatography, Platt & Co. examined with mice sperm which biochemical processes run during gestation and which proteins are affected. In the process they discovered that the reaction of phosphate molecules in the sperm plays a relevant role. The scientists were not only able to identify the phosphate molecules with their technology but also their degree of phosphorylation of amino acids emphasizes Platt. Phosphorylation represents the most important regulation of biological processes in a cell.
On- and off-switch for the capacitation process
“It is important that we can identify special locations of phosphorylation in sperm proteins with our method functioning like switches turning the capacitation process on and off”, as Platt explains to DocCheck. “This information puts us in a position to practice molecular medicine.” It means that the target is not to inactivate an entire protein but to control only sub-processes of phosphorylation with the advantage to avoid undesirable side effects. Platt is convinced that an initial realization of his research results will be used in contraception. Currently the researchers are repeating their analysis with an even more targeted method: The Electron Transfer Dissociation (ETD). Their target: To locate hundreds, if not thousands, of phosphorylation sites during the gestation process of sperm. Recent results were published in the Journal of Proteome Research.