engleski

Impaired rat testicular development caused by 5-azacytidine

AIM OF THE STUDY : 5-azacytidine is a known demethylation agent which can be incorporated into DNA instead of cytosine and prevent its methylation. Therefore, its incorporation into DNA can change the established pattern of gene activation and influence the differentiation. We tried to investigate the influence of demethylation on various tissues in young rats by i.p. application of 5-azacytidine. METHODS: 13 day-old rats were i.p. injected with 5 and 10 mg/kg 5-azacytidine three times during one week. Rats were sacrified after four weeks and testicles fixed in 4% glutaraldehyde, postfixed in 1% OsO4 and embedded in Durcopan. Semi-thin sections were analysed with light microscopy and transmission electron microscopy was done on ultra-thin sections. RESULTS: 13 day-old rats showed impaired testicular development with disturbed spermatogenesis in both sets of experiments. The development was more disturbed with the higher dose of 5-azacytidine. In the affected testicles, some seminiferous tubules were deprived of spermatogenic cells. A number of tubules showed desquamation and disorganisation of seminiferous epithelium. Sertoli cells displayed huge vacuoles and incresed presence of lipid droplets in their cytoplasm. Ultrastructural investigation of mentioned vacuoles demonstrated their low-electron density. CONCLUSION: In the present study it was shown that the process of methylation is crucial for spermatogenesis as well as testicular development in the postnatal period of the rat. It is speculated that 5-azacytidine has a stage-specific effect on the development of spermatogenic cells in the rat.

5-azacytidine; rat testis; development

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