A Vasculature-Associated Niche for Undifferentiated Spermatogonia in the Mouse Testis

Abstract

Mammalian spermatogenesis produces numerous sperm for a long period based on a highly potent stem cell system, which relies on a special microenvironment, or niche, that has not yet been identified. In this study, using time-lapse imaging of green fluorescent protein-labeled undifferentiated spermatogonia (A(undiff)) and three-dimensional reconstitution, we revealed a biased localization of A(undiff) to the vascular network and accompanying Leydig and other interstitial cells, in intact testes. Differentiating spermatogonia left these niche regions and dispersed throughout the basal compartment of the seminiferous epithelium. Moreover, rearrangement of A(undiff) accompanied the vasculature alteration. We propose that the mammalian germline niche is established as a consequence of vasculature pattern formation. This is different from what is observed in Drosophila or Caenorhabditis elegans, which display developmentally specified niche structures within polarized gonads.

Gdnf signaling pathways within the mammalian spermatogonial stem cell niche

“…The niche microenvironment is provided by the somatic Sertoli cells, the basement membrane and cellular components of the interstitial space between the seminiferous tubules. More specifically, these extrinsic signals include growth factors produced by Sertoli cells (Simon et al, 2007), adhesion molecules linking the SSCs to basement membrane components such as laminin (Orwig et al, 2002), and stimuli from the vascular network and interstitial cells (Yoshida et al, 2007). Spermatogonial stem cells are located at the periphery of the seminiferous epithelium, in contact with the basement membrane and Sertoli cells.…”

Pluripotency of Male Germline Stem Cells

“…The major contributor to the SSC niche is Sertoli cells, although the effects of Leydig and myoid cells are not negligible (Yoshida et al, 2007). Sertoli cells reside in the seminiferous tubules in close contact with spermatogonia.…”

“…A vasculature-associated niche also plays critical roles in maintaining undifferentiated spermatogonia in the mouse testes (Yoshida et al, 2007). Undifferentiated spermatogonia preferentially reside in a specific area of the basal compartment within the seminiferous tubules.…”

“…Undifferentiated spermatogonia preferentially reside in a specific area of the basal compartment within the seminiferous tubules. This niche is located adjacent to interstitial somatic cells and blood vessels (Yoshida et al, 2007). Differentiating spermatogonia migrate out of this stem cell niche and are dispersed throughout the entire basal compartment.…”

Downregulation of Col1a1 induces differentiation in mouse spermatogonia

“…1 Previous studies have shown that spermatogenesis involves the detachment of spermatogonia from the basement membrane and their subsequent migration towards the lumen of seminiferous tubules. 2,3 Although mechanisms underlying the maintenance and selfrenewal of SSCs have been explored by many research groups, 1-3 the signaling molecules that mediate the decision of SSCs to differentiate rather than self-renewal remain largely unknown. The balance between self-renewal and differentiation of SSCs must be tightly controlled to maintain normal homeostasis in the normal seminiferous epithelium.…”