The neural cell adhesion molecule (NCAM) provides clues to the development of testicular Leydig cells.

As previously shown, Leydig cells in culture dramatically up-regulate the expression of the neural cell adhesion molecule (NCAM) gene and express alternatively spliced forms. Because the family of NCAM adhesion molecules is known to be involved in cell migration and differentiation, we examined the potential involvement of NCAMs in Leydig cell differentiation in the developing testis. We detected NCAM-immunoreactive cells in the rat and mouse at embryonic day (ED) 13-14 in epithelia of mesonephric tubules and cell clusters between the mesonephros and testis. At about ED 17-18, strongly NCAM-immunoreactive cells were demonstrated extending from the mesonephros/mesonephric tubules into the region occupied by the forming rete testis and spreading into the testis itself. Within the testis, interstitial fetal Leydig cells, identified with an antiserum directed against P450-side-chain cleavage enzyme, were also NCAM immunoreactive, although to a lesser degree, and in part expressed NCAM-associated polysialic acid. In situ hybridization histochemistry demonstrated the presence of NCAM mRNA, mainly in the cell population corresponding to the strongly immunoreactive cells. NCAM forms with molecular weights of 140 and 180 kDa, the latter polysialylated, predominate in immunoblots of fetal testes. Because testicular development occurs along the mesonephros, from which precursor cells are thought to migrate into the developing gonad and then differentiate into the various testicular cell types, our results may suggest that the expression of NCAMs and NCAM modification are associated with cells that appear to migrate into the developing testis. Although it remains to be proven whether these cells could be precursor cells of Leydig cells, this assumption is supported by the fact that within the developing testis, NCAMs and NCAM modifications are expressed during differentiation of testicular P450-side-chain cleavage enzyme-positive Leydig cells. Thus, the adhesion molecule NCAM and its variants and modifications are expressed in the developing testis and may be of functional, "morphogenic" importance. Because Leydig cells in vitro and during fetal development express NCAMs, these molecules may prove to be a suitable specific marker for the study of Leydig cell development and differentiation.