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Development of an in vitro Implantation Model

MIVI (Murine in vitro implantation) model

The aim of the "MIVI model" project is to establish synthetic embryos, so-called embryoids, which represent a physiological and functional in vitro model of mammalian embryogenesis.

This involves the formation of cell aggregates from three distinct cell populations that can be distinguished at the blastocyst stage: 1) the epiblast - from which the fetus develops, 2) the trophectoderm - from which the placenta originates, and 3) the primitive endoderm - from which the yolk sac is formed. Since important steps of embryonic development take place during the implantation into the uterus, a suitable endometrial model system will be developed in parallel. Both components will be characterized by molecular biology and imaging methods, such as live cell microscopy and two-photon fluorescence microscopy.

Using the MIVI model to identify harmful substances

A successful establishment of the embryonic and endometrial models will allow the identification of harmful substances that interfere with embryonic development or successful implantation. The embryoids can be used as a pre-screening tool to test chemical substances for embryotoxic properties which could avoid some of the studies in animals. Furthermore, the model can be used for basic research in developmental biology, i.e. to identify and study mechanisms of cell communication and specific signaling pathways. To date, a large proportion of these questions have been investigated using animal experiments. In addition to the expected possible replacement of some of these animal experiments, the model enables insights into processes of implantation that have so far been completely inaccessible in vivo.

The MIVI model can be used as an extension of the Embryonic Stem Cell Test (EST) developed at the BfR to improve the testing of chemical substances for embryotoxic properties and thus also contribute to a reduction of animal numbers.

In Vitro-Embryoid nach drei Tagen in Kultur mit den drei verschiedenen Zellpopulationen
In vitro embryoid after three days in culture with the three different cell populations: Embryonic stem cells (blue), extraembryonic trophoblast stem cells (red) and XEN cells (green).

Further reading:

Ban, Z., Knöspel, F., & Schneider, M. R. (2020). Shedding light into the black box: Advances in in vitro systems for studying implantation. Developmental Biology, 463(1), 1–10. https://doi.org/10.1016/j.ydbio.2020.04.003

Knöspel, F., Ban, Z., Schönfelder, G., & Schneider, M. R. (2019). Next milestone in understanding early life-blastoids mimic embryogenesis in vitro. Biology of Reproduction, 100(1), 11–12. https://doi.org/10.1093/biolre/ioy182

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