German Research Foundation (DFG) - Project number: 432447433
In human reproductive medicine, the success of assisted reproductive technologies is frequently associated with the quality of oocytes. In order to increase implantation success, much research has been done in the past. In general, the quality of an oocyte is determined by its morphology. However, the use of such criteria is controversial, as morphological features, which are often interpreted as signs of developmental dysfunction, can only be artefacts of natural variability. Therefore, future objectives must be the identification of alternative and much more objective measures to select not only the best oocytes but also their appropriate stages of maturation to achieve the highest fertilisation potential.
In the context of cell biology, mechanical properties are known to be an excellent indicator of the physiological state of a cell in terms of e.g. disease or differentiation. This is exactly where the present research project takes effect. The combination of competencies in biomechanics (applicant Böl) and reproductive medicine (applicant Töpfer) implements a unique and highly innovative approach, which allows the comprehensive characterisation of individual oocytes and the derivation of important information on cell mechanical behaviour in order to assess their quality.
Therefore, the present research project has two main objectives. On the one hand, a biphasic constitutive model will be developed to describe the mechanical behaviour of oocytes before and after fertilisation. On the other hand, new approaches to the micromechanical, experimental sampling of oocytes are being developed, established, and applied to oocytes of different ages. Due to this combination of model development and new experimental methods, a significantly improved understanding of cell mechanics in general but also in sense of oocyte quality is to be expected, which is not yet available.
In particular, new experimental methods are to be developed that allow the sampling of oocytes under various deformation states, such as axial/biaxial tension, compression, indentation, and inflation. This large number of different experiments enables the mechanical identification of the individual components of oocytes as well as the validation of the modelling approach.
On the side of mechanics, the development of a model, which, based on the new experiments on unfertilised and fertilised oocytes, takes into account, among other things, the complex microstructure of the zona pellucida represents a significant gain in knowledge. With the development of a meaningful model, it will be possible to gain a better, more in-depth understanding of load transfer mechanisms that take place in the oocyte (and here in particular in the zona pellucida).
Further, based on the developed model it will be possible to generate virtual scenarios that are experimentally unrealisable. This will help to establish relations between mechanics and cell physiology, e.g., in terms of oocyte quality.