DEVELOPMENT OF AN OVIDUCT-ON-A-CHIP MODEL FOR BETTER BIOMIMICKING THE IN VIVO EARLY EMBRYO DEVELOPMENT

Orateur : Bart M. GADELLA (Utrecht University, The Netherlands)

Millions of children have been conceived using assisted reproductive technologies (ART). Most of the research in the field of ART only focuses on increasing the low efficiency of obtaining and maintaining pregnancy or live birth, whereas the long-term impact on the health of the resulting child has been relatively neglected. Animal models have highlighted that in vitro embryo culture is not exactly mimicking embryo development in the female genital tract and also has effects after embryo transfer on subsequent offspring development and health. In vivo, the oviduct hosts the first embryo developmental period coinciding with a complete reprogramming of its (epi)genome in preparation for the reacquisition of (epi)genetic marks. However, within the ART procedure sperm and oocyte as well as the early embryo have not been in contact with the oviduct. Our work focused on developing an oviduct-on-a-chip platform, which was tested as a more bio-mimic model that may serve to better understand the mechanisms related to epigenetic and genetic reprogramming. The oviduct-on-a-chip device was found to support the conditioning of an apical fluid compartment that allowed exclusive monospermic fertilization (60 % efficiency) and more physiological (in vivo-like) zygote (epi)genetic reprogramming of these fertilized oocytes than under conventional IVF. In the development of the device, specific issues such as release of toxic components from the bio-fabricated materials and affinity of these materials for bioactive components such as steroids should be considered. The created prototype of the oviduct-on-a-chip can, beyond embryo production, be used for several other aspects like screening for effects imposed by toxic components, aberrant metabolic conditions, or as tumorgenic cell culture model. Its use for embryo production can also become useful for biobanking of embryos for endangered mammalian species in which routine ART fails.

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