The role of Hic1 in testicular smooth muscle cells

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Testicular smooth muscle cells, including peritubular myoid cells and vasculature smooth muscle cells, regulate spermatogonial stem cell function in the mammalian testis. However, the mechanisms and signaling pathways that affect germ cell function largely remain to be elucidated. Here we report the expression of Hypermethylated in cancer 1 (Hic1) in testicular smooth muscle cells by using the Hic1CreERT2:RosatdTomato mice. Linage tracing experiments with Hic1CreERT2:RosatdTomato mice revealed that Hic1 expressing peritubular myoid expanded their population throughout testicular development. We hypothesized that Hic1 expression in testicular smooth muscle cells is involved in maintenance of spermatogenesis and tested this hypothesis by using aSMACreERT2:Hic1flox:RosatdTomato mice that allow conditional knock out (cKO) of Hic1 in smooth muscle cells. Deletion of Hic1 in smooth muscle cells resulted in aberrant spermatogenesis with degenerate seminiferous epithelium and dilated seminiferous tubules in mouse testis. The Hic1 cKO mice had heavier testes with more undifferentiated spermatogonia and fewer differentiated germ cells compared to controls. The peritubular myoid cells surrounding the seminiferous tubules were distributed at similar density in cKO and control mice, yet the number of Sertoli cells per seminiferous tubule in cKO mice was decreased compared to the control mice. Deposition of fibronectin, an extracellular matrix protein secreted from peritubular myoid cells, was disrupted in Hic1 cKO mice, suggesting a functional defect in Hic1 cKO peritubular myoid cells. Additionally, a tight junction protein, occludin, showed a disruption in cKO mice, indicating an indirect effect of cKO peritubular myoid cells on the germ cells, through Sertoli cells. Taken together, we demonstrated that Hic1 signaling in testicular myoid cells is playing an important role to regulate spermatogenesis. This study demonstrated the expression of Hic1 in testicular smooth muscle cells and provided insights into a signaling pathway in testicular smooth muscle cells to directly/indirectly affect germ cells.
Testis, Mouse, Smooth muscle cells, Hic1
Uchida, A. (2018). The role of Hic1 in testicular smooth muscle cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from doi:10.11575/PRISM/33135