The knowledge of the chemical structures that govern the processes associated with fertility — more specifically with the fertilisation process — opens up new possibilities for intervention, with as yet unknown consequences.
A recent article published in the journal Current Biology (1 – Ver AQUÍ) presents new findings on the mechanism by which the sperm and egg can mutually recognize each other during the fertilization process, allowing the adhesion and penetration of the sperm through the membrane of the egg, as a preliminary step for the chromosomal crossover of both gametes and the generation of a new human being.
The aforementioned study, conducted by investigators from the Karolinska Institute (Stockholm, Sweden), provides data on the three-dimensional chemical structure of an egg membrane receptor called Juno, improving our understanding of how this receptor interacts with the corresponding sperm membrane protein, in the manner of a lock and key.
The discovery of both egg and sperm “signalling” proteins was published two years ago in the journal Nature,2 in a study that established the relationship between two proteins, named “Izumo1” in the sperm and “Juno” in the egg. The investigators observed that, after the sperm enters the egg — possible only after the interaction of the aforementioned proteins Juno and Izumo1 — the Juno receptor is shed from the egg membrane in a rapid reaction aimed at blocking the entry of any other sperm attempting to fertilize it.
A previous study published in 20073 found that the increased calcium ion concentration in the membrane of the egg plays a crucial role for first and successive cell divisions in the fertilisation process, leading towards embryo development.
According to the investigators at the Karolinska Institute, the results suggest that modifications of an ancestral vitamin B9 (folic acid) receptor occurred a long time ago in the evolution of species, which gave rise to a key interaction, essential for mammalian reproduction: the binding of egg and sperm membranes, leading to the fusion of the gametes.
The up- and downsides of the new discovery about fertilisation process
The new finding opens the door to the investigation of certain cases of sterility, in which there may be a malfunction of the interactive process of both proteins, Juno in the egg and Izumo1 in the sperm. Knowledge of their three-dimensional chemical structure could allow processes that modify it to be designed in the future, in order to restore their functionality in the event that is altered (a situation that would prevent fertilisation process).
Equally however, being able to make structural changes in both proteins could lead to the opposite phenomenon: introducing structural modifications such that they become inactive again, unable to perform their vital function of permitting the process of fertilisation of the egg by the sperm.
This, it seems, could be the application that the authors of this discovery have in mind, i.e. the design of a new contraceptive method in which hormone treatments that alter the woman’s menstrual cycle or the ovulatory process would not be necessary, because it would no longer be imperative to prevent the encounter between sperm and egg. What it would achieve is that, should this encounter occur, neither would be able to synchronise the processes that lead to fertilisation, as a result of a problem in the coupling of both signalling proteins, one of which would have been previously altered.
Although today this is mere conjecture, knowledge of the chemical structures that govern the processes associated with fertility — more specifically with the phenomenon of fertilisation — opens up new possibilities for intervention, with as yet unknown consequences. While this offers a beacon of hope in the case of correcting certain fertility issues, it nevertheless raises serious questions in the bioethical plane when targeted at modifications that lead to sterility for contraceptive purposes, with unknowns regarding the reversibility of the process and onset of undesirable effects that might be associated with these procedures.
References
1. Han L, Nishimura K, Al Hosseini HS, Bianchi E, Wright GJ, Jovine L. Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion of mammalian gametes. Current Biology, online 8 February 2016
2. Bianchi E, Doe B, Goulding D, Wright GJ. Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature 2014;508(7497),483-7.
3. Jessus C, Haccard O. Fertilization: Calcium’s double punch. Nature 2007;449:297-8 doi:10.1038/449297a; Published online 19 September 2007
Julio Tudela
Bioethics Observatory.
Catholic University of Valencia
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