Reelin regulates male mouse reproductive capacity via the sertoli cells

Abstract

Reelin plays important roles in brain development. Reeler mutant mice that lack the protein reelin (RELN) suffer from cell type‐ and region‐dependent changes in their neocortical layers, and adult reeler mutant mice have dilated seminiferous tubules. Meanwhile, the mechanism by which Reelin regulates the spermatogenic cell development in mice and their reproductive abilities remains unclear. In the present study, we used reeler mutant mice to investigate the effects of Reelin on reproduction in mice. The results indicated variations in sex hormone expression among the reeler mice, indicating that they produce few offspring and their spermatogenic cells are irregularly developed. Moreover, glial cell line‐derived neurotrophic factor (GDNF)/GDNF family receptor alpha 1, Ras/extracellular regulated protein kinases (ERK), and promyelocytic leukemia zinc finger (PLZF)/chemokine (C‐X‐C motif) receptor 4 (CXCR4) serve as potential regulatory pathways that respond to the changes in sertoli cells and the niche of male germ cells. Our findings provided valuable insights into the role of reeler in the reproductive abilities of male mice and development of their spermatogonia stem cells.

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

“…Accumulating studies have indicated that various signaling pathways in SCs are implicated with spermatogenesis 27,28 . Until now, numerous signaling pathways have been found in Sertoli cells, including the androgensignaling pathway 29,30 , the AMP-activated protein kinase (AMPK) signaling pathway 31 , the follicle stimulating hormone (FSH)/adenylate cyclase/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway 32 , the Hippo signaling pathway 33,34 , the intergrin mediated signaling pathway 4,35 , the Janus kinase/signal transducer and activator of transcription signaling pathway 36,37 , the mitogen-activated protein kinases (MAPK) signaling pathway [38][39][40][41][42][43][44] , the nuclear factor kappa B signaling pathway 45,46 , the nitric oxide/soluble guanylyl cyclase/cyclic guanosine monophosphate/ protein kinase G signaling pathway 47,48 , the Notch signaling pathway 49 , the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3k)/AKT serine/threonine kinase (Akt) signaling pathway 50,51 , the Sonic Hedgehog signaling pathway 52,53 , the transforming growth factor-β (TGF-β)/ Smad signaling pathway 54 , and the Wnt signaling pathway 55,56 (Table 1). Among all these signaling pathways, the TGF-β/Smad, AMPK, and MAPK signaling pathways have attracted much more attentions in the past decade.…”