Naslov
Oxidative stress elicited by a DNA-demethylating teratogen 5-azacytidine in the mammalian placenta can be alleviated by antioxidant pretreatment

Autori
Sobočan, Nikola ; Katušić-Bojanac, Ana ; Himelreich-Perić, Marta ; Sinčić, Nino ; Krasić, Jure ; Šerman, Ljiljana ; Ježek, Davor ; Bulić-Jakuš, Floriana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
European journal of human genetics, 30 (2022), Suppl 1 / - , 2022, 344-344

Skup
54th European society of human genetics conference (ESHG 2021)

Mjesto i datum
Online, 28.08.2021. - 31.08.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
oxidative stress ; placenta ; embryo ; methylation

Sažetak
Introduction: Our experiments showed that the DNA- demethylating epigenetic drug 5-azacytidine (5azaC) is a teratogen causing oxidative stress and intrauterine growth restriction (IUGR), alleviated in rat fetuses by an antioxidant- pretreatment. We hypothesized such effects will be confirmed in the placenta. Materials and Methods: On day 12 and 13 of gestation, Fisher rat dams received intravenously N-tert- Butyl-α- phenylnitron (PBN) (40 mg/kg) and one hour later intraperitoneally 5azaC (5mg/kg) or only 5azaC. Controls received PBN or were untreated. Placentas were isolated on the gestation day 15 and day 20. Immunohistochemical signals of the Proliferating Cell Nuclear Antigen (PCNA) and markers of oxidative/nitrosative processes (8-oxoDG and nitrotyrosine, respectively) were stereologically quantified by the numerical density (Nv). The apoptotic index was calculated, and DNA- methylation was assessed by pyrosequencing. Results: Pretreatment with PBN of 5azaC-treated dams during the trophoblast invasion and intense proliferation phases significantly improved the weight of 15- and 20-days old placentas. In 20- days-old placentas, the apoptotic index and Nv of 8-oxoDG and nitrotyrosine were significantly higher in placentas of dams treated by 5azaC than in those pretreated with PBN. Nv for PCNA was significantly lower in all placentas of 5azaC- treated dams than in controls. Conclusions: In the placenta, we confirmed the association of DNA- demethylating agent's growth restriction with oxidative/nitrosative stress. These experimental results are of importance for understanding the mechanism of intrauterine growth restriction (IUGR) and its prevention by antioxidant activity. Financed by EU project, ERDF, Operational Programme Competitiveness and Cohesion, No. KK.01.1.1.01.0008, Reproductive and Regenerative Medicine - Exploring New Platforms and Potentials.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA