Male Paediatric Fertility Restoration using Testis Organoids

Chemotherapy treatments for cancer and haematological disorders can lead to male infertility. While adult males can freeze a sperm biopsy prior to chemotherapy, pre-pubertal children cannot do so, as they do not yet produce sperm. Reaching 88% survival rate for paediatric cancers nowadays, many of these kids will survive to adulthood but remain infertile. There are currently no clinical fertilityrestoration options available for these kids. Many of them are advised to undergo a testis biopsy procedure for fertility preservation prior to chemotherapy, with the hope that techniques will be developed to allow the use of these samples for future sperm production.Within the ERC StG, we aimed to develop an in vitro system that can closely model the testis. As such, we have recently published the development of testis organoids from both embryonic and prepubertal mouse testis. These organoids can be cultured in vitro for 9 weeks, while preserving all cell types normally present in the testis. These organoids highly recapitulate the in vivo state by creatingstructures, as well as presenting expression profiles, of in vivo testis. We developed defined media composition for in vitro maturation. Finally, we show indications that meiosis is initiated in vitro within the organoids.In this ERC PoC, building on our development in the mouse, we will generate human testis organoids derived from pre-pubertal testis biopsies that were obtained prior to chemotherapy treatment. We will assess the ability of these testicular cells to create human testis organoids, and analyse the structure, transcriptome, as well as ability to initiate, and potentially complete, meiosis. Within Restore-Fertility, we aim to achieve significant progress with the technology development in human samples, and provide a proof-of-concept for sperm production in vitro. We will also achieve business progression by consolidating IP strategy, market analysis, and develop a comprehensive business strategy.