Restoration of fertility by light

The research presented by the scientists from the “Center of Advanced European Studies and Research” was based on the application of so called optogenetics. The idea is to insert genes encoding light-sensitive proteins into the chosen cells. The area in which optogenetics is of particular interest is neuroscience, where the functions of genetically sensitized to light neurons can be monitored or even modulated.

In this study, a gene coding for photoactivated adenylyl cyclase (AC) was introduced into mice lacking this enzyme. AC catalyzes the conversion of adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). Importantly, cAMP is involved in the activation of sperm motility, hence, it strongly contributes to proper functioning of the sperm cells.

Sperm of mice lacking AC enzyme is most often not capable of moving that results in infertility. When sperm with the introduced gene was subjected to blue light, cells could produce cAMP, regained motility and most important, were able to fertilize eggs. Interestingly, the light-sensitive AC has been discovered in soil bacteria.

PD Dr. Dagmar Wachten from the “Center of Advanced European Studies and Research”, who is a coauthor of the presented study, depicts how optogenetics can be used for investigation of mechanisms responsible for infertility as well as its treatment, and in what other fields it can be useful.

Do you think that it would be possible to apply “optogenetic” approach with the use of light for treating infertile people?

Dagmar Wachten: To treat infertile patients, we first need to understand how sperm work and what is going wrong when they are infertile. This we do in animal models, preferably in mice. Here, optogenetics is a very useful tool because it allows to investigate signaling pathways in sperm with high spatial and temporal resolution independent of any side-effects that e.g. pharmacological tools cause. In mice, we have shown that optogenetics can be used to restore fertility. However, in humans, this approach might not be feasible for different reasons: 1) the current in vitro fertilization methods are already well established with reasonably high success rates; 2) for applying optogenetics, one needs to know what is going wrong in the sperm from these infertile men, because the different optogenetic tools only allow to control distinct signaling pathways – however, for most of the patients, it is not known, which defect these sperm have. Thus, it is even more important to understand the signaling pathways in healthy sperm and then apply this knowledge for the diagnosis of infertile men.

Would such treatment involve “gene therapy” in the meaning that genes encoding light-sensitive enzymes would be introduced to human cells?

Dagmar Wachten: In principal yes. To control cellular activity by light, cells need to be engineered with a light-sensitive molecule. This is fairly easy in cell culture in the lab and also in whole animals e.g. mice, flies or fish, this is not too difficult due to the recent advances in genetical engineering. In case of infertile men, however, this would require a gene therapy approach combined with in vitro fertilization because somehow, the sperm would need to be stimulated by light. Although it might be difficult to apply optogenetics for the treatment of infertility, there have been already attempts made in different fields to apply optogenetics to humans using gene therapy.

In what other medical areas such approach might be also beneficial?

Dagmar Wachten: There are different approaches published already how optogenetics might be used for the treatment of different diseases. The most prominent approach seems to be to treat patients with Retinitis pigmentosa. Retinitis pigmentosa is a hereditary disease of the retina that leads to incurable blindness. Gene therapy based on optogenetics has already been shown in animal models to restore sensitivity to light. Similar approaches have been used to improve cochlear implants in animal models with light activating the hearing system. 

Sources:

http://www.ncbi.nlm.nih.gov/pubmed/25601414

http://www.genengnews.com/gen-news-highlights/light-activated-sperm-restore-fertility/81250828/

by Maciej Smolarz