Genome integrity maintenance during spermatogonial development

The specific aim of this thesis was to unravel the mechanisms that determine and regulate the dynamic response to DNA damage during spermatogonial development, with a specific focus on the role of the structural maintenance of chromosomes (SMC) 5/6 complex. The development of spermatogonial stem cell (SSC) culture, together with the development of CRISPR-Cas9, now for the first time open up the possibility to study this using spermatogonia-specific genome modification. In the current thesis, we combined an established culture system for spermatogonial proliferation and differentiation with the CRISPR-Cas9 system to knock out genes of interest in the response to DNA damage. Furthermore, we additionally addressed the broad and potentially large clinical prospects and implications of using CRISPR-Cas9 to treat spermatogenic failure or to prevent the transmission of genetic abnormalities to human offspring by transplantation of genetically modified human SSCs.