Nils Trost

Sexual reproduction is the only way for mammals to create offspring – and it is the primary way for many other animals. It creates diversity in a population by combining gametes and thereby genetic information of both parents. Gonadogenesis creates ovaries or testes, sexually dimorphic organs that produce the female or male gametes and involves the processes of sex determination and differentiation. Given their essential role in the survival of the species, the large observed diversity of these processes is surprising. Spermatogenesis in the adult testis was shown to evolve rapidly and its unique transcriptional landscape promotes the emergence of new genes. This was formulated in the “out of the testis” hypothesis. However, the evolutionary dynamics of oogenesis remain less understood. Furthermore, many insights on gonadogenesis have come from mouse models. Considering the fast evolution of gonads, the applicability of these findings to the human process is imperfect – especially in regard to disorders/differences of sex development (DSD). In my dissertation work, I set out to improve our understanding of primate gonadogenesis and its evolutionary dynamics. For this, I analysed at the single cell level the chromatin accessibility and transcriptome of human and marmoset female and male prenatal gonadogenesis, including a sample from a developing testis of a foetus with Klinefelter syndrome (XXY).
My thesis work advances the understanding of primate gonadogenesis and its disorders, by characterizing regulatory and expression changes during prenatal development. My evolutionary analyses provide insights into the evolution of gonadal cell types and present oogenesis as a birthplace of new genes.

The testis is a key male reproductive organ that produces gametes through the process of spermatogenesis. Testis morphologies, sperm phenotypes, and the process of spermatogenesis evolve rapidly in mammals, presumably due to the evolutionary pressure on males to give rise to their own offspring. Here, we review studies illuminating the molecular evolution of the testis, in particular large-scale transcriptomic studies, which were based on bulk tissue samples and, more recently, individual cells. Together with various genomic and epigenomic data, these studies have unveiled the cellular source, molecular mechanisms, and evolutionary forces that underlie the rapid phenotypic evolution of the testis. They also revealed shared (ancestral) and species-specific spermatogenic gene expression programs. The insights and available data that have accumulated also provide a valuable resource for the investigation and treatment of male fertility disorders – a dramatically increasing problem in modern industrial societies.

Data analysis based on enrichment of Gene Ontology terms has become an important step in exploring large gene or protein expression datasets and several stand-alone or web tools exist for that purpose. However, a comprehensive and consistent analysis downstream of the enrichment calculation is missing so far. With WEADE we present a free web application that offers an integrated workflow for the exploration of genomic data combining enrichment analysis with a versatile set of tools to directly compare and intersect experiments or candidate gene lists of any size or origin including cross-species data. Lastly, WEADE supports the graphical representation of output data in the form of functional interaction networks based on prior knowledge, allowing users to go from plain expression data to functionally relevant candidate sub-lists in an interactive and consistent manner.