Embryonic mouse testis development: role of platelet derived growth factor (PDGF-BB).

Abstract

Platelet-derived growth factors (PDGFs) are paracrine growth factors mediating epithelial-mesenchymal interactions and exerting multiple biological activities which include cell proliferation, motility, and differentiation. As previously demonstrated, PDGFs act during embryonic development and recently, by culturing male genital ridges, we have demonstrated that PDGF-BB is able to support in vitro testicular cord formation. In the present paper, we report that PDGF-BB is present during embryonic testis development and, in organ culture, induces cord formation although with reduced diameters compared with the cords formed in the genital ridges cultured in the presence of HGF. Moreover we have analyzed the roles exerted by this growth factor during the morphogenesis of the testis. We demonstrate by immunohistochemical experiments that PDGF-BB and its receptors are synthesized by the male UGRs isolated from 11.5 and 13.5 dpc embryos and by Western blot that the factor is secreted in a biologically active form by testicular cells isolated from 13.5 dpc embryos. The biological roles of the factor have also been studied and we demonstrate that PDGF-BB acts as a migratory factor for male mesonephric cells whose migration is a male specific event necessary for a normal testicular morphogenesis. In addition we demonstrate that during testicular development, PDGF-BB induces testicular cell proliferation being in this way responsible for the increase in size of the testis. Finally we demonstrate that PDGF-BB is able to reorganize dissociated testicular cells inducing the formation of large cellular aggregates. However the structures formed in vitro under PDGF-BB stimulation never had a cord-like morphology similar to the cord-like structures formed in the presence of HGF (Ricci et al., 2002, Mech Dev 118:19-28), suggesting that this factor does not act as a morphogenetic factor during testicular development. All together the data presented in this paper demonstrate that PDGF-BB and its receptors (alpha- and beta-subunits) are present during the crucial ages of embryonic mouse testis morphogenesis and indicate the multiple roles exerted by this factor during the development of the male gonad.