Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - MechBiolRep (Mechanobiology of Bovine Reproduction)

Teaser

The growth of ovarian follicles, maturation of oocytes and preimplantation embryo development are reproductive processes that are implicated with the application of mechanical forces and major changes on the physical properties of the surrounding microenvironments. Despite the...

Summary

The growth of ovarian follicles, maturation of oocytes and preimplantation embryo development are reproductive processes that are implicated with the application of mechanical forces and major changes on the physical properties of the surrounding microenvironments. Despite the association with mechanical inputs, the mechanobiological aspects of female reproductive physiology is poorly understood. This ERC project aims at revealing the relationship between the physical processes and cell-fate decision-making that direct and regulate mammalian reproduction.

Due to obvious ethical reasons, availability of human biological material is problematic and limited. Hence, we focus on a bovine model which is an excellent mimic of human preimplantation development. In addition, bovine reproduction by itself is of great importance in terms of global food supply. Both the dairy industry and the beef industry depend on bovine fertility (only pregnant cos produce milk). While worldwide demand of dairy products is surging, cow fertility is declining, where oocyte developmental potential is a major factor. We expect to elucidate mechanistic understanding of bovine reproduction, which will contribute to the dairy industry by making it more efficient, thus increasing food production by fewer cows. The outcome of this project is expected to be further implemented in human clinical treatments to improve in vitro fertilization – embryo transfer procedures.

The objectives of this ERC project are to reveal the mechanobiological aspects of bovine reproduction. We aim at understanding how changes in the mechanical properties of the ovary affect follicle growth and oocyte maturation. Such mechanical changes are implicated with normal ageing and disease. We aim at understanding how changes in the mechanical properties of the oocytes correlate and direct their potential to become fertilized. Finally, we aim at understanding how the changes in the mechanical properties of the embryos correlate and regulate their potential to develop and to implant within the uterus.

Work performed

Intracytoplasmic sperm injection turned into a powerful tool to select embryos for transfer
We have developed computational algorithms that elucidate the viscoelastic properties of the cytoplasmic mass of human oocytes during in vitro fertilization via intracytoplasmic sperm injection (ICSI). ICSI is a now standard clinical procedure that is routinely practiced in IVF clinics and also is relevant for reproduction schemes of domestic animals. Using video recordings of this procedure, we can now score the potential of oocytes to become fertilized, to undergo preimplantation embryo development and to implant in the uterus.

Oocyte and embryo mechanics:
We have designed novel devices that facilitate continuous assessment of the viscoelastic properties of oocytes during in vitro maturation and embryos during preimplantation development. These methods are non-invasive and are performed inside incubators that maintain optimal culture conditions that are used for example in IVF clinics. We are starting to define the mechanical regimes that are indicative of oocytes and embryos that have the capacity to develop and generate a pregnancy.

Introducing artificial intelligence into IVF clinics
We harnessed advanced deep learning tools to generate fully automated embryo classification algorithms. Our classifiers are trained on video recordings of embryos undergoing preimplantation development inside time-lapse incubators (which are broadly distributed in IVF clinics worldwide). Our algorithms are more accurate than existing tools and provide a standardized fully automated tool that substitutes the clinical staff.

Final results

Our project highlights a mechanobiological perspective of mammalian reproductive biology. Our approach is “beyond the state of the art” in the field. We developed novel devices and instruments that allow real time mechanical evaluation of oocytes and embryos and provided a proof of concept that demonstrates how the developmental potential of oocytes and embryos can be evaluated based on their physical properties in a noninvasive manner. This approach is compatible with microscopic visualization of preimplantation embryo development. Hence, we also generated deep learning tools to evaluate the potential of embryos to generate a pregnancy. We expect to accurately define the mechanical regimes and the dynamic profiles that are indicative of high developmental quality. The clinical implications of this project are far-reaching. Using our tools, clinicians will be able to select the embryos that will implant in the uterus and generate a live birth. In this manner, IVF treatments will be shorter and safer both for the newborn and for the mother. The financial costs that these tools save can then be invested in other important medical treatments.