Infertility is a prevalent health issue affecting approximately one in six couples during their lifetime. The causes of infertility can be diverse, including developmental abnormalities, diseases, infections, or lifestyle factors. However, in one-third of cases, the cause remains unknown. To treat infertility, it is essential to identify its cause. Therefore, a comprehensive understanding of testicular and ovarian development is necessary. Testicular and ovarian development begin with sex determination, which is the process by which the bipotential gonad differentiates into either a testis or an ovary. To comprehend the whole process of sex determination and gonadal development, it is necessary to understand all the cell populations that interact and act during this process, as well as all the structures that form the differentiated testis or ovary. The rete testis and rete ovarii, two structures found in the testis and ovary, respectively, were described centuries ago. However, their importance in gonadal development has been lost over time. The rete testis is a cavity that connects the seminiferous tubules to the efferent ducts, and its presence is critical for male fertility. Indeed, its absence would result in the inability of spermatozoa to travel to the epididymis and be ejaculated. The function of the rete ovarii is less clear, but it has been reported to play a role in folliculogenesis and may have an excretory function. The impact of the rete ovarii on female fertility is thus still debated. Thus, the origin, development, and function of the rete testis and rete ovarii remain elusive.

In this PhD thesis, I investigated the complexity of the cell population present in both testis and ovary during sex determination and gonadal development. I characterized the Supporting-Like Cells (SLCs), which can differentiate into the rete testis and rete ovarii. Using a lineage tracing mouse model, I demonstrated that SLCs are derived from Pax8⁺ progenitors. I showed that SLCs are located at the interface between the gonad and mesonephros. I could also demonstrate that SLC progenitors can also differentiate into cells of the supporting lineage, Sertoli cells in males and pre-granulosa cells in females. I investigated the role of Pax8 in the fate commitment of the SLC progenitors and showed that in both males and females, the absence of Pax8 results in the absence of rete testis and rete ovarii. In XY gonad, the absence of Pax8 leads to a shift in fate commitment of the SLCs progenitors and their differentiation into cells of the somatic lineages, such as Sertoli cells, Leydig cells, peritubular myoid cells or steroidogenic progenitors instead of SLCs.