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Antioxidant ameliorated negative impact of a DNA- demethylating agent on placental growth and morphology of aged preterm placentas

We showed that a DNA demethylating agent/epigenetic drug 5 azacytidine (5azaC) used in treatment of human malignancies is a teratogen that impaired growth of both embryos and placentas in treated rat dams. The pretreatment with the antioxidant N tert Butyl α phenylnitron (PBN) improved development of rat fetuses. We now investigated whether pretreatment with the antioxidant PBN could improve the placental development/ aging in 5 azaC treated pregnant dams. 12 th and 13 th days of gestation: endovascular trophoblast invasion and intense proliferation of the labyrinth and basal zone. 20 th day of gestation: basal zone regresses and labyrinth fully develops. Conclusion: In preterm placentas (20 days old) PBN pretreatment significantly rescued growth diminished by 5 azaC through lowering the number of apoptotic cells that was associated with a significantly lower amount of cells under oxidative nitrosative stress. DNA demethylating epigenetic drug induces oxidative nitrosative stress in the aged placentas. Because DNA demethylation causing oxidative stress might also be of importance for placental premature aging during human gestation leading to IUGR, we propose further investigation of the antioxidant PBN profilactic activity for the prevention of IUGR.

DNA methylation ; 5azaC ; placenta ; rat

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