Differential Expression of Urocortin in Human Testicular Germ Cells in Course of Spermatogenesis: Role for Urocortin in Male Fertility?

Abstract

To provide the first insights into the potential role of urocortin in mammalian spermatogenesis, we studied the expression of urocortin and corticotropin-releasing factor receptors 1 and 2 in the human testis. Urocortin is a bioactive peptide with antiapoptotic and antiproliferative properties. The proper regulation of apoptosis and proliferation is of high physiologic relevance in the control of spermatogenesis in adulthood and of the noncycling stage of gonocytes in fetal life. Using polymerase chain reaction analysis and immunohistochemistry, the expression and tissue localization of urocortin on mRNA and at the peptide level was studied in 9 normal adult, 5 fetal, and 5 Sertoli cell-only testicular specimens. Tissue localization of corticotropin-releasing factor receptors in normal adults was considered using immunohistochemistry. We found that urocortin mRNA was present in all adult specimens tested and that the urocortin peptide was expressed in elongating spermatids, mature spermatozoa, and peritubular myoid cells, and to a lesser extent in Leydig cells. Corticotropin-releasing factor receptor 1 was mainly expressed in spermatogonia, spermatocytes, and Leydig cells, and corticotropin-releasing factor receptor 2 was mostly expressed in spermatogonia. The antibodies against urocortin produced a nuclear staining in fetal gonocytes. No significant immunopositivity for urocortin could be observed in the Sertoli cell-only specimens. The expression of urocortin in normal adult and fetal testicular germ cells in the cell division arrest phases suggests a probable role for this peptide in the pathophysiology of germ cell differentiation and division. In human germ cells, the separate location of urocortin and its receptors indicates a receptor-independent action of urocortin in the course of spermatogenesis.