title: Inhibition of platelet-derived growth factor actions in the embryonic testis influences normal cord development and morphology.
abstract: Platelet-derived growth factors (PDGFs) are paracrine factors with roles in mesenchymal-epithelial interactions during normal and pathologic processes. Previously, PDGF and its receptor (PDGFR) have been shown to be present in perinatal, peripubertal, and adult rat testes. The role of PDGF in embryonic testicular cord formation is not known. The hypothesis tested is that PDGFs and PDGFRs are expressed during cord formation and that inhibition of their action influences normal cord formation during embryonic testis development. Embryonic Day (E) 13 gonadal organ cultures were used. Organs were cultured for 3 days and treated daily with vehicle or a PDGFR-specific tyrosine phosphorylation inhibitor (i.e., the tyrphostin AG1295 or AG1296). Vehicle-treated testes formed normal cords, whereas tyrphostin-treated testes formed "swollen cords," a phenomenon characterized by a significant decrease in the number of cords per testis area and increased cord diameter due to fusion of cords. Expression of PDGF and PDGFR in E13, E14, E16, Postnatal Day (P) 0, and P20 testes was examined. Messenger RNAs for PDGF-A and -B and PDGF alpha- and beta-receptors were expressed in isolated testes during all developmental periods examined. Immunoreactivity for PDGF was present throughout the testicular compartment at E14, restricted primarily to testicular cords at E16, and present in cells of the testicular cords with a stronger immunoreactivity in certain interstitial cell types of P0 testis. PDGFR beta-receptor immunoreactivity was primarily localized to the mesonephros of E14 organs and the testicular interstitium of E16 and P0 testes. Tyrphostins did not affect apoptotic cell number in the testis. PDGF had no effect on cell growth in P0 testis cultures. The results show that PDGFs and PDGFRs are expressed in embryonic testis during cord formation in a tissue-specific manner. Inhibition of PDGF actions does not inhibit cord formation but does alter normal cord development and morphology. The observations provide insight into the factors involved in male sex differentiation and embryonic testis development.
authors.affiliation: Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4231, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Uzumcu
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Dirks
authors.forename: Michael K
authors.initials: MK
authors.lastname: Skinner
mesh_terms: D000818:Animals; D017209:Apoptosis; D000077214:Becaplermin; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D008297:Male; D008650:Mesonephros / Q000737:chemistry; D009924:Organ Culture Techniques; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000235:genetics; D012671:Seminiferous Tubules / Q000196:embryology*; D013737:Testis / Q000737:chemistry / Q000187:drug effects / Q000196:embryology*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: C407689:6,7-dimethoxy-2-phenylquinoxaline; D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D020032:Tyrphostins; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D011505:Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor