Downregulation of Col1a1 induces differentiation in mouse spermatogonia

Col1a1 (one of the subunit of collagen type I) is a collagen, which belongs to a family of extracellular matrix (ECM) proteins that play an important role in cellular proliferation and differentiation. However, the role of Col1a1 in spermatogenesis, especially in the control of proliferation and differentiation of spermatogonial stem cells (SSCs), remains unknown. In this study, we explored effects of downregulation of Col1a1 on differentiation and proliferation of mouse spermatogonia. Loss-of-function study revealed that Oct4 and Plzf, markers of SSC self-renewal, were significantly decreased, whereas the expression of c-kit and haprin, hallmarks of SSC differentiation, was enhanced after Col1a1 knockdown. Cell cycle analyses indicated that two-thirds of spermatogonia were arrested in S phase after Col1a1 knockdown. In vivo experiments, DNA injection and electroporation of the testes showed that spermatogonia self-renewal ability was impaired remarkably with the loss-of-function of Col1a1. Our data suggest that silencing of Col1a1 can suppress spermatogonia self-renewal and promote spermatogonia differentiation. Asian Journal of Andrology (2012) 14, 842-849; doi: 10.1038/aja.2012.66; published online 15 October 2012