Expression and role of PDGF-BB and PDGFR-β during testis morphogenesis in the mouse embryo

Abstract

The role played by PDGF in testis morphogenesis is still incompletely understood. The present study investigates the expression and potential role of platelet-derived growth factor-BB (PDGF-BB) and its receptor, PDGF receptor β (PDGFR-β), during mouse testis cord formation, and the possibility that the growth factor may be involved in the migration to the gonad of mesenchymal cells of mesonephric origin. Studies from this laboratory have previously shown that mesenchymal cells that migrate from the mesonephros into the gonad, to form peritubular myoid cells and most of the intertubular cells, can be identified by the presence on their surface of the p75 neurotrophin receptor (p75NTR), and can be isolated to near-purity by immunomagnetic selection with anti-p75NTR antibody. We show here that mesonephric p75NTR(+) cells also bear the PDGFR-β, and are able to migrate and proliferate in vitro in response to PDGF-BB. PDGF-BB is expressed at higher levels in male than female developing gonads, suggesting a role for this factor in testis development. Such a role is further supported by the observation that addition of PDGF-BB to serum-free medium is sufficient to allow organ-cultured male 11.5 days post-coitum urogenital ridges to form testis cords. Finally, we show that mesonephric cell motility and growth induced by exposure to PDGF-BB involve mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways, as MAPK inhibitor U0126 and PI3K inhibitor Ly294002 inhibit migration and proliferation in vitro assays. The present findings support the hypothesis that the PDGF/PDGFR system plays a key role in testis morphogenesis in the mouse embryo.

Fibroblast growth factor (FGF) 2 and FGF9 mediate mesenchymal–epithelial interactions of peritubular and Sertoli cells in the rat testis

“…Dose-response studies indicated that maximal effects of FGF2 were seen with the dose of 50 ng/ml. This finding was consistent with previous publications examining the mitogenic or regulatory function of FGF2 (Hoeben et al 1999, Van Der Wee & Hofmann 1999, FGF9 (Colvin et al 2001) or PDGF (Uzumcu et al 2002, Puglianiello et al 2004, Ricci et al 2004) on testicular cells. Hence, this dose of 50 ng/ml was chosen for the next experiments for each of the growth factors studied.…”

Platelet-Derived Growth Factor Receptor β-Subtype Regulates Proliferation and Migration of Gonocytes

“…Previous in vitro studies suggested a role for PDGF-B and PDGFR-␤ during prenatal mouse testis development (37)(38)(39). However, examination of testis from PDGFR-␤ Ϫ/Ϫ mice at E13.5 by Brennan et al (10) and our analysis of PDGFR-␤ and PDGF-B null mice gonads at E18.5 revealed no overt defects, ruling out a critical role for this receptor during prenatal testis development.…”

Expression and functional role of hepatocyte growth factor and its receptor (c-met) during fetal mouse testis development

“…Several growth factors are involved in embryonic testicular differentiation such as transforming growth factors (Olaso et al 1998, Cupp et al 1999a,b, Levine et al 2000, neurotrophins (Cupp et al , 2002 and insulin (Nef et al 2003) and we have reported the involvement of an isoform of platelet-derived growth factor (PDGF-BB) in testis cord organization this factor being able to support testicular cord formation in vitro (Ricci et al 1999(Ricci et al , 2004. In a recent paper we have shown, in parallel with other authors, that a and b subunits of the platelet-derived growth factor receptors (PDGFR) are expressed in the differentiating male urogenital ridges and that PDGF-BB is synthesized and secreted by the testis during its embryonic differentiation (Puglianiello et al 2004, Ricci et al 2004). In addition, we have demonstrated that PDGF-BB induces mesonephric cells migration and modulates the functional activities of the testicular cells increasing testicular cell proliferation and reorganizing dissociated testicular cells into large cellular aggregates (Ricci et al 2004).…”