APOPTOSIS IN ADULT-MOUSE TESTIS INDUCED BY EXPERIMENTAL CRYPTORCHIDISM

Induction of cryptorchidism in the mouse causes infertility due to dis ruption of spermatogenesis including reduction of germ cells; however, the cellular mechanism responsible for the degenerative changes in cr yptorchid testis is still unclear. In surgically induced bilateral cry ptorchidism of 3-month-old C57BL/Tw mice, cellular changes in the cryp torchid testis were studied 1, 2, 3, 7, 14 and 21 days after the opera tion by electron microscopy, DNA fragmentation, in situ 3'-end labelin g, serum and testicular testosterone measurements and gene expression. Although the testis showed DNA fragmentation even in intact mice, the cryptorchidism increased the degree of the fragmentation at 1 postcry ptorchidism (p.c.) day. Apoptosis was encountered mainly in spermatids and spermatocytes. The number of apoptotic cells in the cryptorchid t estis showed a 7-fold increase at 1 p.c. day as compared to the intact testis, then it gradually decreased. Serum testosterone levels showed a significant decrease at 2 p.c. days and remained low thereafter. Ex pression of transforming growth factor-beta(2) (TGF-beta(2)), TGF-beta (3), tumor necrosis factor-alpha receptor and Fas mRNAs increased in t he crypt orchid testis within 24 h after the operation. In lpr(cg) and lpr mice lacking functional Fas, gld mice lacking functional Fas liga nd and lpr(cg)-gld mice lacking both functional Fas and Fas ligand, th e experimental cryptorchidism also induced apoptosis in germ cells at 1 p.c. day, The present results indicate that cryptorchidism induces a poptotic dell death in germ cells, and that testosterone reduction and the Fas system may not be significantly involved in the apoptosis of male germ cells.