Apoptosis in adult mouse testis induced by experimental cryptorchidism.
Induction of cryptorchidism in the mouse causes infertility due to disruption of spermatogenesis including reduction of germ cells; however, the cellular mechanism responsible for the degenerative changes in cryptorchid testis is still unclear. In surgically induced bilateral cryptorchidism of 3-month-old C57BL/Tw mice, cellular changes in the cryptorchid testis were studied 1, 2, 3, 7, 14 and 21 days after the operation by electron microscopy, DNA fragmentation, in situ 3'-end labeling, 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 postcryptorchidism (p.c.) day. Apoptosis was encountered mainly in spermatids and spermatocytes. The number of apoptotic cells in the cryptorchid testis 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. Expression of transforming growth factor-beta 2 (TGF-beta 2), TGF-beta 3, tumor necrosis factor-alpha receptor and Fas mRNAs increased in the cryptorchid testis within 24 h after the operation. In lpr(cg) and lpr mice lacking functional Fas, gld mice lacking functional Fas ligand and lpr(cg)-gld mice lacking both functional Fas and Fas ligand, the experimental cryptorchidism also induced apoptosis in germ cells at 1 p.c. day. The present results indicate that cryptorchidism induces apoptotic 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.
Ohta
Y
Y
Department of Veterinary Science, Faculty of Agriculture, Tottori University, Japan. ohta@agr.tottori-u.ac.jp
Nishikawa
A
A
Fukazawa
Y
Y
Urushitani
H
H
Matsuzawa
A
A
Nishina
Y
Y
Iguchi
T
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D003456:Cryptorchidism / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009929:Organ Size; D012671:Seminiferous Tubules / Q000473:pathology; D013094:Spermatozoa / Q000473:pathology; D013737:Testis / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure