Nature of the Spermatogenic Arrest in Dazl −/− Mice

Abstract

Dazl encodes an RNA-binding protein essential for spermatogenesis. Mice that are deficient for Dazl are infertile, lacking any formation of spermatozoa, and the only germ cells present are spermatogonia and a few spermatocytes. 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. Both 5-bromodeoxy-uridine incorporation and mitotic index indicated that the remaining A spermatogonia were actively proliferating. C-kit immunohistochemical studies showed that most of the A spermatogonia were positively stained for the c-Kit protein (∼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 concluded that the prime spermatogenic defect in the Dazl −/− mice is a failure of the great majority of the A_al spermatogonia to differentiate into A₁ spermatogonia. As a result, most seminiferous tubules of Dazl −/− mice only contain actively proliferating A_s, A_pr, and A_al spermatogonia, with cell production being equaled by apoptosis of these cells.