Shooting blanks: manipulating fertility in men
17 Jul, 2012
Researchers from Scotland, Bulgaria and Australia have identified a gene, called Katnal1, that is responsible for sperm maturation.
Manipulating gene Katnal1 can correct male infertility
When the protein produced by the gene is absent, sperm in the testes remain immature and infertile. The researchers believe the manipulation of this gene using drugs can act as either a male contraceptive or conversely to correct male infertility when this gene is involved. This type of non-hormonal treatment would offer a reversible alternative to current (quite unpopular) male contraceptives that affect testosterone levels and can cause irritability, mood swings and acne.
Research used genetic mapping and DNA sequencing
The research, published on 25 May 2012 in the journal PLoS Genetics, involved feeding drugs to mice to give them random genetic mutations. Next, the researchers identified any infertile mice in the group. To trace the infertility back to the responsible gene mistake, the researchers used genetic mapping techniques to first identify which chromosome the responsible gene was situated within and then DNA sequencing to identify the mutation. Once the gene was identified, they looked at its specific effect on the mice sperm cells.
Absence of a protein results in release of immature sperm
Using a technique called antibody detection, the researchers were able to work out that, in the testis, the gene (when it is functioning correctly) produces a protein in particular cells, called Sertoli cells, in both mice and humans. They determined that the role of the protein in these cells was to control microtubules and to retain sperm until they reached maturity – the absence of this one protein from the Sertoli cells results in premature release of immature sperm and male infertility.
The researchers write that the identification and characterisation of this gene will further our understanding of how male fertility is promoted while also providing important information relevant to the development of male contraceptives.
Aim is to develop drugs that turn Katnal1 on and off
Researchers may now be able to develop drugs that can turn Katnal1 on and off. If this is achievable, it should be possible to create a form of non-hormonal birth control for men. It may also be possible to use gene therapy (replacement of faulty genes) to cure any infertility that results from the gene not working and conversely to turn the gene off permanently – a kind of genetic vasectomy.
The researchers say that there are no doubt other genetic mutations associated with infertility that affect the supporting cells (and not the sperm themselves) that are yet to be identified but treatments may be available with 10 years.
- 17 July 2012