Spermatogenesis is a complex differentiation process that produces millions of genetically unique sperm cells every day. During spermatogenesis the developing germ cells undergo metamorphic changes as they transform from primitive spermatogonial stem cells to large meiotic spermatocytes, divide into smaller round spermatids and finally become streamlined, compact sperm. Each cell type has a unique transcriptional profile. Early cells of spermatogenesis, especially meiotic spermatocytes express massive amounts of transcripts while transcription is completely halted later due to the nuclear condensation of spermatids. To cope with these transcriptomic challenges, large cytoplasmic ribonucleoprotein granules called germ granules appear and provide dynamic platforms for the transcripts and their regulators to come together.

Here, two proteins of the largest germ granule, the Chromatoid Body (CB), were selected for investigation: the autophagosome transporting FYCO1 and the RNA degrading endonuclease SMG6. Two mouse lines were created to reveal the roles of these germ granule components in spermatogenesis. The results show that FYCO1 is needed for the integrity of germ granules. CB morphology was disrupted in the absence of FYCO1, a phenotype that worsened under stress conditions. Nonetheless FYCO1 depleted mice were fertile. Conversely, the deletion of the second component, endonuclease SMG6, lead to infertility. The results showed that SMG6 is required for the transcriptional balance of developing germ cells which it regulates together with the piRNA pathway. Both studies highlight the importance of germ granules in spermatogenesis.

Overall, this thesis comprises three studies. First, a simple BSA-gradient method to isolate round spermatids and spermatocytes from mice using standard laboratory equipment was developed to facilitate the two main studies of this thesis work. In the first of these studies FYCO1 was identified as a link between autophagy and the CB while the second revealed the role of the endonuclease SMG6 in spermatogenesis and male germ cells transcriptional integrity. Together these two studies contribute to revealing the functions of the enigmatic germ granules and the pivotal roles they play for the maintenance of male fertility.