Computational modelling has been used to describe the molecular interactions occurring at the exact moment of fertilisation, shedding light on a range of unanswered questions in fertility research.
Researchers from ETH Zurich, Switzerland, used the Swiss National Supercomputing Centre's 'Piz Daint' supercomputer to model the initial binding between sperm and egg at a molecular level. In turn, their findings could have implications for infertility treatment and the development of novel contraceptive methods.
'The simulations provide a more detailed picture of the dynamics of the interactions' said Professor Viola Vogel, who led the study published in the journal Scientific Reports. She also clarified the importance of their computational approach, stating that 'the findings that we derive from [the simulations] would hardly be possible based on the static crystal structures of the proteins.'
At its core, the initial interaction between the sperm and egg cells is governed by two proteins: JUNO, which appears on the egg cell, and IZUMO1, which is on the sperm cell surface. While it was known that their binding was essential for cell fusion, the exact mechanism had not been established.
The insights made by the scientists were enabled by modelling these protein interactions within an aqueous environment, in which the water molecules altered the proteins' structures and functionality.
The researchers were able to use their computer simulations to generate further insights into the molecular dynamics of the first moments of fertilisation. For example, they found that zinc ions alter the structure of IZUMO1, stopping it from binding with JUNO. They suggest that this is one reason why a flood of zinc ions, known as a 'zinc spark' is released by the egg cell post-fertilisation, as this prevents further penetration by other sperm cells.
Additionally, they found that folates, such as folic acid, were able to bind with JUNO after it had bound with IZUMO1. Experiments in the lab had found no binding between folates and JUNO alone, despite it being a folate receptor. Folic acid supplements are recommended at the beginning of pregnancy to support healthy neuronal development.
The authors concluded in their paper. 'Our findings provide fundamentally new, high-resolution insights into the dynamics of the central molecules that mediate the first specific sperm-egg recognition event,' and that their research '… might inspire the community to evaluate how to better predict or treat infertility… or how to improve on in vitro fertilisation techniques.'