Spatiotemporal patterns of expression of neurotrophins and neurotrophin receptors in mice suggest functional roles in testicular and epididymal morphogenesis

Several reports have established that the action of neurotrophins is not re stricted to the nervous system but can affect a broad range of non-neuronal cells. Nerve growth factor (NGF) is present in adult testis and has been s uggested as a potential regulator of meiosis in rat seminiferous epithelium . Here we present an extensive immunohistochemical study on neurotrophins a nd their receptors (p75 and trk) in the developing mouse testis and epididy mis, and in fetal human testis. During the early steps of testicular and ep ididymal organization in the mouse, strong p75 immunoreactivity is detectab le in the gonadal ridge in the mesenchyme that is excluded from the evolvin g testicular cords, and in the mesenchymal cells of the mesonephros. Later in organogenesis, most of the p75-positive interstitial cells of the testis coexpress neurotrophin-3 (NT-3) and the truncated trk B receptor in a deve lopmentally regulated pattern. Our Western blot data confirm the expression of these molecules. These findings suggest that neurotrophin receptors pla y a role in early inductive events during critical periods of testicular an d epididymal development. During fetal and postnatal histogenesis, an incre asing number of NT-3- and p75-positive mesenchymal cells start to express o r-smooth muscle isoactin, suggesting a role for the so-called neurotrophic system in the differentiation of testicular myoid cells and epididymal smoo th muscle cells. In the testis of an 18-wk gestational-age human fetus, imm unohistochemical analysis has shown intense immunoreactivity of mesenchymal cells to antibodies for neurotrophin receptors p75, trk A, and trk C, and their ligands NGF and NT-3. In addition, we found that in the human fetal t estis, the interstitial cells that are differentiating into peritubular myo id cells are associated with a dense network of nerve fibers. Our data sugg est that neurotrophins and their receptors are involved in a multifunctiona l system that regulates cell differentiation and innervation in the develop ing testis and epididymis.