Organoïde modellen van vrouwelijk voortplantingsweefsel om hun biologie en ziekte te bestuderen

The female reproductive system is highly prone to diseases of which many aspects remain elusive. In this thesis, we focused on ovarian cancer (OC) and endometriosis, two major gynecological disorders. OC is the 5th most common cause of cancer in women and the most lethal gynecological malignancy worldwide, while endometriosis represents a highly burdening disease characterized by out-of the uterus (ectopic) presence of endometrial-like tissue affecting 1 in 10 women of reproductive age. Existing (in vitro) research models are limited in applicability and clinical translatability. Hence, robust and reliable in vitro models are needed to better understand the mechanisms underlying the diseases' pathogenesis. Here, we aimed at establishing and applying new in vitro 3D models to study OC and endometriosis by adopting the organoid technology. First, we developed new OC organoid models starting from patient-derived biopsies. The organoids showed patient tumor-dependent morphology and disease characteristics, and recapitulated marker expression and mutational landscape of the original tumor. Second, we applied organoids from endometriosis patients to start deciphering underlying pathobiological mechanisms. Third, we developed a new human in vitro embryo implantation model using endometrial organoids, called 'open-faced endometrial layer' (OFEL). Addition of embryo models (blastoids) showed attachment upon hormonal priming of the endometrial cells. This new implantation model can now be applied to deliver deeper insight into the embryo-endometrium crosstalk and to explore endometrium-centered causes of sub-/infertility in endometriosis patients.