Endocrine Abstracts

Unlike most organs whose fate is pre-determined, mammalian gonads are unique as they originate from a pair of bipotential genital ridges that can develop as either ovaries or testes depending on which genetic program is activated during embryonic life. The discovery of genes important for sex determination, notably SRY/SOX9 in the testis and FOXL2/WNT4 in the ovary, has benefited from the study of human disorders of sex development (DSD) and animal models, such as the mouse. However, half of DSD cases typically remains undiagnosed. Advances in next-generation sequencing technologies have enables the genome-wide profiling of ovaries and testes during the window of sex determination, down to single cell level, thus providing a comprehensive overview of which genes are expressed and what is the chromatin epigenetic status at critical developmental stages. Together with the advent of CRISPR-Cas9 technology, a powerful genome editing tool, these technologies have allowed to uncover the role of the noncoding genome, which represents 98% of the human genome, in controlling conserved sex determination pathways. Recent data have also demonstrated that female sex determination is not a default pathway but an active, gene-directed process which must be maintained active throughout life. Interaction proteomics approaches have been used to dissect the molecular mechanism of sex maintenance in the ovary thus allowing the identification of the critical players that safeguard the ovary from ovary-to-testis transdifferentiation in adulthood. The latest developments in the application of omics technologies to the investigation of sex determination and gonadal development pathways will be discussed in this session.