8-Iso-PGF(2alpha) administration generates dysmorphogenesis and increased lipid peroxidation in rat embryos in vitro.
BACKGROUND
Diabetic pregnancy displays increased incidence of congenital malformations and elevated levels of lipid peroxides in the offspring. The aim of the present work was to study if exogenous administration of one lipid peroxide, the isoprostane 8-iso-PGF(2alpha), is teratogenic per se in rat embryos in vitro, and if such teratological effects may be diminished by supplementation of an antioxidative agent, i.e., N-acetylcysteine or superoxide dismutase, to the culture medium.


METHODS
Day-9 embryos were cultured in vitro for 48 hr and subjected to 8-iso-PGF(2alpha) with and without N-acetylcysteine or superoxide dismutase.


RESULTS
Addition of 2 micromol/l of the isoprostane 8-iso-PGF(2alpha) to the culture medium caused high malformation rate, decreased protein and DNA contents, decreased somite number and crown-rump-length as well as marked accumulation of the isoprostane in the embryonic tissues. Adding N-acetylcysteine or superoxide dismutase to the culture medium with isoprostane normalized almost all morphological and biochemical parameters, including the elevated tissue concentration of 8-iso-PGF(2alpha).


CONCLUSIONS
Results indicate that the isoprostane (8-iso-PGF(2alpha)) serves both as an oxidative stress indicator and a teratogenic agent. The findings support earlier studies of enhanced oxidative stress and increased malformation rate in embryos exposed to a diabetes-like environment, and suggest prevention of dysmorphogenesis by administration of antioxidative agents.
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003470:Culture Media / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives*; D004622:Embryo, Mammalian / Q000187:drug effects*; D028441:F2-Isoprostanes / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D015227:Lipid Peroxidation; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D019170:Somites / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013723:Teratogens; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000975:Antioxidants; D003470:Culture Media; D028441:F2-Isoprostanes; D016166:Free Radical Scavengers; D013723:Teratogens; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D013482:Superoxide Dismutase; D000111:Acetylcysteine