Testicular organoids to study cell-cell interactions in the mammalian testis

Abstract

Background: Over the last ten years, three-dimensional organoid culture has garnered renewed interest, as organoids generated from primary cells or stem cells with cell associations and functions similar to organs in vivo can be a powerful tool to study tissue-specific cell-cell interactions in vitro. Very recently, a few interesting approaches have been put forth for generating testicular organoids for studying the germ cell niche microenvironment.

Aim: To review different model systems that have been employed to study germ cell biology and testicular cell-cell interactions and discuss how the organoid approach can address some of the shortcomings of those systems.

Results and conclusion: Testicular organoids that bear architectural and functional similarities to their in vivo counterparts are a powerful model system to study cell-cell interactions in the germ cell niche. Organoids enable studying samples in humans and other large animals where in vivo experiments are not possible, allow modeling of testicular disease and malignancies and may provide a platform to design more precise therapeutic interventions.

Keywords: cell-cell interaction; germ cell niche; morphogenesis; testicular organoids.

Figure 1:. Schematic representation of the germ cell niche.

Undifferentiated germ cells including spermatogonial stem cells are localized at the basement membrane and remain in close contact with the Sertoli cells inside the seminiferous epithelium. Peritubular myoid cells line the outer perimeter of the basement membrane and Leydig cells, vascular cells and testicular macrophages are located in the interstitium. As spermatogonia differentiate, they traverse the tight junctions and move from the basal to the adluminal compartment of the seminiferous epithelium.

Figure 2:. An approach to use testicular organoids in biomedical research.

Genetically modified or treated germ cells are seeded on a pre-made organoid with non-treated testicular cells and assessed for outcomes such as survival, self-renewal and spermatogenesis.

Figure 3:. Schematic representation of testicular organoids to study development.

Different testicular cells can be derived from iPS cells to generate testicular organoids.