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Expression of Platelet-Derived Growth Factor-A (PDGF-A), PDGF-B, and PDGF Receptor- and -ß during Human Testicular Development and Disease

Dipartimento di Fisiopatologia Medica (S.B., S.M., M.A., G.S., L.G.) and Dipartimento di Medicina Sperimentale e Patologia (C.D., A.M.), Università di Roma "La Sapienza", Policlinico Umberto I, 00161 Rome, Italy; Dipartimento di Medicina Sperimentale, Università di L’Aquila (S.U., N.R., E.A.J.), 67100 L’Aquila, Italy; and Dipartimento di Medicina Interna, Cattedra di Endocrinologia, Università di Modena e Reggio Emilia, Policlinico di Modena (C.C.), 41100 Modena, Italy

Address all correspondence and requests for reprints to: Lucio Gnessi, M.D., Ph.D., Dipartimento di Fisiopatologia Medica, Policlinico Umberto I, Università di Roma "La Sapienza", 00161 Rome, Italy. E-mail: . lucio.gnessi{at}uniroma1.it

Abstract

Platelet-derived growth factor (PDGF) plays a critical role in regulating the development and functional control of various tissues and has been implicated in the pathogenesis of serious diseases, including cancer and atherosclerosis. Given the emerging role of PDGF in the development and function of male gonads, we compared the expression profiles of the mRNAs of the PDGF A- and B-chains and of the PDGF receptor (PDGFR) - and ß-subunits in fetal and adult human testis. The immunohistochemical localization of the corresponding proteins in fetal, adult, and diseased human testicular tissues was also analyzed. PDGFs and PDGFRs mRNAs were readily detected by both Northern analysis and RT-PCR. The transcript levels were higher during 16–20 wk gestation, significantly lower at 24–28 wk, and increased in the adult. An identical pattern of protein expression was confirmed by immunohistochemistry, although the cellular localization of the PDGF system changes during postnatal development, concomitantly with the progression of spermatogenesis. In the testicular samples from patients affected by either complete aplasia of germ cells or various grades of spermatogenic arrest, the immunohistochemical localization of PDGFs and PDGFRs was different from normal, confirming a close connection between germ cells and PDGF system distribution. These results indicate that PDGF, through complex interactions, could play a leading role in ontogenesis and testicular pathophysiology in humans. Finally, the expression of PDGF ligands and receptor proteins in Leydig cell tumors suggests a relationship of the PDGF system to tumorigenesis or tumor progression in this testicular neoplasm.

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