Emerging organoid models to study the epididymis in male reproductive toxicology

The importance of the epididymis on sperm maturation and consequently male fertility has been well documented. The pseudostratified epithelium of the epididymis is comprised of multiple cell types, including principal cells, which are the most abundant, and basal cells. The role of basal cells has been unclear and has been a source of discussion in the literature. However, the recent demonstration that these cells are multipotent or adult stem cells has opened new areas of research in epididymal biology. One such avenue is to understand the regulation of these stem cells, and to exploit their properties to develop tools for toxicological studies to elucidate the effects of chemicals on cell differentiation and epididymal function in vitro. Studies in both rat and mouse have shown that purified single epididymal basal cells cultured under 3D conditions can proliferate and differentiate to form organoids, or mini organs. Furthermore, these epididymal basal stem cells can self-renew and differentiate into other epididymal cell types. It is known that during epididymal development, basal cells are derived from undifferentiated columnar cells, which have been reported to share common properties to stem cells. Like basal cells, these undifferentiated columnar cells can also form organoids under 3D culture conditions and can differentiate into basal, principal and clear cells. Organoids derived from either basal cells or columnar cells offer unique models for toxicology studies and represent an exciting and emerging approach to understand the epididymis.