Women who survive childhood cancer often fail to conceive because their eggs are damaged by (gonadotoxic) chemotherapy. A major breakthrough has been the possibility to cryopreserve cortical strips of their ovarian tissue for autologous transplantation later in life. This has led to over 100 successful pregnancies worldwide, including in the Netherlands. However, the risk of reintroducing cancer cells with the ovarian graft in patients with previous hematopoietic malignancies is too great and alternatives are needed.
The objectives of OVOGROWTH include:
Benchmark human oogenesis using single-cell technology. We will systematically generate transcriptional profiles of oocytes and other cells in the human ovary both during development and adulthood, to identify cellular components and cellular trajectories.
Understand how follicle maturation is regulated in humans ex vivo. We hypothesise that vasculogenesis plays a role regulating follicle maturation in the ovary. We will test this in an existing xenotransplantation (mouse) model in the lab using patient-specific ovarian tissue and endothelial cells (ECs) to recreate the physiological niche.
Recapitulate follicle maturation in vitro. Using different 3D-scaffolds (natural and synthetic), we aim to systematically characterize and optimize the progression of primordial human follicles (both oocyte and granulosa cells) during maturation in vitro.
Mini-ovaries to understand follicle assembly in vitro. We propose to generate mini-ovary organoids from human foetal gonads to clarify the progression of germ cells into primordial follicles and track for the first time the emergence of the granulosa cells, which so far remains elusive. Understanding these initial steps will be crucial to utilize iPSCs in the mini-ovary organoid system.