Involvement of the D-type cyclins in germ cell proliferation and differentiation in the mouse

Using immunohistochemistry, the expression of the U-type cyclin proteins wa s studied in the developing and adult mouse testis. Both during testicular development and in adult testis, cyclin D-1 is expressed only in proliferat ing gonocytes and spermatogonia, indicating a role for cyclin D-1 in sperma togonial proliferation, in particular during the G(1)/S phase transition. C yclin D-2 is first expressed at the start of spermatogenesis when gonocytes produce A(1) spermatogonia. In the adult testis, cyclin D-2 is expressed i n spermatogonia around stage VIII of the seminiferous epithelium when A(al) spermatogonia differentiate into A, spermatogonia and also in spermatocyte s and spermatids. To further elucidate the role of cyclin D-2 during sperma togenesis, cyclin D-2 expression was studied in vitamin A-deficient testis. Cyclin D-2 was not expressed in the undifferentiated A spermatogonia in vi tamin A-deficient testis but was strongly induced in these cells after the induction of differentiation of most of these cells into A(1) spermatogonia by administration of retinoic acid. Overall, cyclin D-2 seems to play a ro le at the crucial differentiation step of undifferentiated spermatogonia in to A(1) spermatogonia. Cyclin D-1 is expressed in both proliferating and qu iescent gonocytes during testis development. Cyclin a), expression was foun d in terminally differentiated Sertoli cells, in Leydig cells, and in sperm atogonia in adult testis. Hence, although cyclin D-3 may control G(1)/S tra nsition in spermatogonia, it probably has a different role in Sertoli and L eydig cells. In conclusion, the three D-type cyclins are differentially exp ressed during spermatogenesis. In spermatogonia, cyclins D-1 and D-3 seem t o be involved in cell cycle regulation, whereas cyclin D-2 likely has a rol e in spermatogonial differentiation.