engleski

Inheritance of epigenetically induced changes of the male gonad in two generations of rats

Influence of DNA-demethylation on the rat male gonad of different developmental stages (foetal to adult) was investigated and followed in progeny of treated parents during two generations. Fisher rats were treated with 5 or 10 mg/kg body weight of 5-azacytidine. Pregnant females were treated intraperitoneally on 12th day of pregnancy. Adult males were treated twice a week during five weeks. 13-days-old male and female rats were treated three times and their offspring was mated at the age of two months. Male gonads were weighted and processed for classical histology, stereological analysis or transmission electron microscopy. In gonads of treated foetuses significantly lower number of germ cells in mm3 of tissue (Nv= numerical density) was found. Male adult gonads were significantly smaller. Gonads of 13-days-old treated were significantly smaller. In some seminiferous tubules severe atrophy and a loss of stratification within germinative epithelium was found. Affected tubules contained only spermatogonia and spermatocytes without spermatides and mature sperms. Survival of the progeny was affected only in the first generation. First generation males showed the same disturbed pattern of spermatogenesis as their treated parents. In the second generation all seminiferous tubules were affected and only occasionally few spermatogonia and spermatocytes were found. Our experiments lead to the conclusion that male gonads are always affected by DNA demethylation. Moreover, epigenetically caused change is transgenerationaly passed to the progeny of treated parents. Second generation was even more affected regarding male gonad development which was in contrast to survival, affected only in the first generation rats.

DNA; Demethylation; Male gonad; Epigenetics

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