Modelling of normal and abnormal implantation in 3D primary endometrial organoids

Pregnancy strictly depends on successful implantation, i.e. embedding of the embryo into the lining of the womb. This lining, known as the endometrium, protects and nourishes the embryo and allows the formation of the placenta. When perturbed, aberrant implantation leads to a spectrum of disorders, including implantation failure, miscarriage and late pregnancy complications, such as preeclampsia. Therefore, a precise understanding of the early interactions between the embryo and the endometrium may reveal new ways to prevent common ad devastating pregnancy disorders.

Unfortunately, modelling human implantation is complex. Ethically, it is impossible to study this process in women, and animal models have major limitations. Therefore, we aim to develop a new model that uses stem cells isolated from endometrial biopsies from specific patients. These cells form 3D structures (called organoids), akin to endometrium, when provided with a scaffold in the form of a gelatinous matrix (Matrigel). The aim of this project is
to develop these novel structures into the most advanced model of human embryo implantation. First, we will investigate how closely these structures resemble the endometrium and test if we can trigger the expression receptivity genes in response to hormonal treatment. Second, by comparing the interactions of human embryos (donated to research by IVF couples) with organoids established from different patients, new insights into the causes of reproductive failure will emerge.

In order to achieve these aims, interdisciplinary skills drawing from medicine, biology and physics, such as microfluidics and quantitative imaging using a range of microscopy techniques, will be central to this project.