Nature of the spermatogenic arrest in Dazl -/- mice

Dazl encodes an RNA-binding protein essential for spermatogenesis. Mice tha t are deficient for Dazl are infertile, lacking any formation of spermatozo a, and the only germ cells present are spermatogonia and a few spermatocyte s. To gain more insight regarding the timing of the spermatogenic arrest in Dazl -/- mice, we studied the spermatogonial cell types present in testis sections and in seminiferous tubular whole mounts. Most of the seminiferous tubular cross-sections contained A spermatogonia as the most advanced cell type, with only very few containing cells up to pachytene spermatocytes. B oth 5-bromodeoxy-uridine incorporation and mitotic index indicated that the remaining A spermatogonia were actively proliferating. C-kit immunohistoch emical studies showed that most of the A spermatogonia were positively stai ned for the c-Kit protein (similar to 80%). The clonal composition of the A spermatogonia in tubular whole mounts indicated these cells to be A(single ) (A(s)), A(paired) (A(pr)), and A(aligned) (A(al)) spermatogonia. It is co ncluded that the prime spermatogenic defect in the Dazl -/- mice is a failu re of the great majority of the A(l), spermatogonia to differentiate into A , spermatogonia. As a result, most seminiferous tubules of Dazl -/- mice on ly contain actively proliferating A(s), A(pr), and A(al) spermatogonia, wit h cell production being equaled by apoptosis of these cells.