STAGE-SPECIFIC DEGENERATION OF GERM-CELLS IN THE SEMINIFEROUS TUBULESOF NONOBESE DIABETIC MICE

The cause of fertility problems in insulin-dependent diabetes is large ly unknown. To evaluate the role of autoimmunity-associated phenomena in the testis as a possible cause of the derangement in spermatogenesi s, the stage-specific apoptosis of germ cells in the insulitis phase o f pre-diabetes was quantified in the testes of non-obese diabetic (NOD ) mice. The seminiferous epithelium of normal BALB/c and NOD mice cont ained cells positive for in-situ end-labelling (ISEL) of DNA. ISEL-pos itive germ cells formed clusters in the seminiferous epithelium of the NOD mice in marked contrast to the seminiferous epithelium of the BAL B/c mice, which contained only individual cells positive for ISEL. ISE L-positive cells were present in the basal and luminal compartments of the epithelium. Ultrastructural analysis and demonstration of externa lized phosphatidyl serine confirmed that the cells were undergoing apo ptosis. The ultrastructurally apoptotic cells included spermatogonia, spermatocytes and spermatids. In cytological squash preparations of se gments of seminiferous tubules from NOD mice aged 17-20 weeks, the num ber of ISEL-positive cells/mm tubule was significantly lower in segmen ts at stages I-II of the seminiferous epithelial wave but higher at st ages III-IV in comparison to BALB/c mice. The numbers of ISEL-positive cells/mm tubule in the other stages were similar in the two strains o f mice. Analysis of P-32-3'-end labelled DNA from the testes showed th at the BALB/c mice had relatively more DNA fragmentation than did the NOD mice. These data suggest that autoimmune insulitis in the NOD mice is associated with increased amounts and abnormal stage distribution of apoptosis in the seminiferous epithelium, resulting in derangement of spermatogenesis.