Development and function of smooth muscle cells is modulated by Hic1 in mouse testis

Abstract

In mammalian testis, contractile peritubular myoid cells (PMCs) regulate the transport of sperm and luminal fluid, while secreting growth factors and extra-cellular matrix (ECM) proteins to support the spermatogonial stem cell (SSC) niche. However, little is known about the role of testicular smooth muscle cells during the postnatal testicular development. Here we report age-dependent expression of Hypermethylated in cancer 1 (Hic1, ZBTB29) in testicular smooth muscle cells, including PMCs and vascular smooth muscle cells in mouse. Postnatal deletion of Hic1 in smooth muscle cells led to their increased proliferation and resulted in dilation of seminiferous tubules with increased numbers of PMC. These seminiferous tubules contained fewer Sertoli cells and more spermatogonia, and fibronectin was not detected in their basement membrane. The expression levels of genes encoding smooth muscle contractile proteins, Acta2 and Cnn1, were down regulated in the smooth muscle cells lacking Hic1, and the seminiferous tubules appeared to have reduced contractility. These data imply a role for Hic1 in determining the size of seminiferous tubules by regulating postnatal smooth muscle cell proliferation, subsequently affecting spermatogenesis at adulthood.