ToxSci Advance Access originally published online on February 14, 2008
Toxicological Sciences 2008 103(1):149-157; doi:10.1093/toxsci/kfn027
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reactive Oxygen Species Contribute to Lipopolysaccharide-Induced Teratogenesis in Mice
Department of Toxicology, Anhui Medical University, Hefei 230032, China
1 To whom correspondence should be addressed at Department of Toxicology, Anhui Medical University, Hefei 230032, China. Fax: +86-551-5161179. E-mail: xudex{at}mail.hf.ah.cn.
Received November 30, 2007; accepted February 6, 2008
 |
Abstract |
|---|
Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including embryonic resorption, fetal death and growth retardation, and preterm delivery. In the present study, we showed that an ip injection with LPS daily from gestational day (gd) 8 to gd 12 resulted in the incidence of external malformations. The highest incidence of malformed fetuses was observed in fetuses from dams exposed to 20 µg/kg LPS, in which 34.9% of fetuses per litter were externally malformed. In addition, 17.4% of fetuses per litter in 30 µg/kg group and 12.5% of fetuses per litter in 10 µg/kg group were externally malformed. Importantly, external malformations were also observed in fetuses from dams exposed to only two doses of LPS (20 µg/kg, ip) on gd 8, in which 76.5% (13/17) of litters and 39.1% of fetuses per litter were affected. LPS-induced teratogenicity seemed to be associated with oxidative stress in fetal environment, measured by lipid peroxidation, nitrotyrosine residues, and glutathione (GSH) depletion in maternal liver, embryo, and placenta. alpha-Phenyl-N-t-butylnitrone (PBN, 100 mg/kg, ip), a free radical spin-trapping agent, abolished LPS-induced lipid peroxidation, nitrotyrosine residues, and GSH depletion. Consistent with its antioxidant effects, PBN decreased the incidence of external malformations. Taken together, these results suggest that reactive oxygen species might be, at least partially, involved in LPS-induced teratogenesis.
Key Words: lipopolysaccharide; teratogenicity; reactive oxygen species.
Lei Zhao, Yuan-Hua Chen, and Hua Wang contributed equally to this work.