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Changes in the placenta and in the rat embryo caused by the demethylating agent 5-azacytidine

Methylation is an important mechanism for regulation of gene expression during vertebrate development. 5-azacytidine is usually used as an experimental tool for demethylation. We have used 5-azacytidine ( 5mg/kg body weight) in different stages of rat development. It was applied in vivo by i.p. injection to pregnant Fischer rat females from day 1 to day 16 of pregnancy. Embryos were isolated and examined the day before birth. After the application of 5-azacytidine on the first three days no changes whatsoever were found. On the fourth day of pregnancy 5-azacytidine caused reduction of growth which was present in all living fetuses found after that day. From day 5 till day 11 of application no living fetuses were found. On day twelve 24% of fetuses survived, but forelimb and hindlimb malformations were present. On the day 13, 5-azacytidine did not interfere with survival, but malformations were still present. From day 14 on, no gross external malformations were found. Placentas were also influenced by 5-azacytidine. They were significantly smaller and histological evaluation showed that labyrinthine part was severely reduced, but on the contrary trophoblast giant cells were more abundant than in controls. These results demonstrate that 5-azacytidine did not affect only the developing embryo, but as well impaired the placenta in a specific manner.

placenta; embryo; rat; methylation; 5azaC

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