Impact of 5-Azacytidine on Placental Weight, Glycoprotein Pattern and Proliferating Cell Nuclear Antigen Expression in Rat

In process of placentation, expression of various glycoproteins has important role in embryonal development. Alterations of DNA methylation caused by 5-azacytidine (5azaC) can disturb normal glycoproteins expression as well as proliferative ability of trophoblast cells. In order to assess that, a single dose of 5azaC was injected intraperitoneally to pregnant rats during the day 1 to 19 of gestation. Animals were sacrificed on the day 20 and placental weights as well as glycoprotein composition were analyzed together with immunohistological assessment the of degree of trophoblast cells proliferation. The placental weight was found significantly smaller in animals treated by 5azaC on the days 4 to 14 of gestation (p<0.01, Student's t test). The treatment on days 4, 5 and 6 resulted in the lack of labyrinth with the strong proliferative activity of the cells in the basal layer. Expression of glycoproteins with molecular mass smaller than 60 kD was reduced on day 6. The 5azaC treatment from day 7 to 10 completely disturbs placental structure and the proliferation of trophoblast cells is poor. During these days GP70 exhibits stronger expression in the treated animals, contrary to GP40 which is stronger in controls. Natural border between labyrinth and the basal layer was established on the days 11 and 12. The basal layer is dominant with lower proliferation of trofoblast cells compared to the controls. With establishment of labyrinth on the day 13, the expression of GP40 was restored. Proliferation of trophoblast cells from day 13 to 15 was higher compared to the controls. The changes of placental mass, proliferative ability of trophoblast cells in rat placenta exposed to 5azaC, represents another proof of the importance of epigenetics in regulation of placental development.