Abstract： Background Preeclampsia,especially early onset of preeclampsia (PE),is a common and serious disorder with high maternal and perinatal morbidity and mortality.Dietary factor is one of the most important factors which may affect the occurrence and development of the disease.The aim of this study is to investigate the effects of dietary factors on pathological changes of liver and placenta in preeclampsia-like mouse model by establishing the model at multiple stages of gestation.Methods Wild-type (WT) mice were injected subcutaneously with nitric oxide synthase (NOS) inhibitor L-arginine methyl ester (L-NAME,50 mg.kg-1.d-1) to establish PE-like model (L-NAME group) at early-,mid-,and late- pregnant periods respectively; simultaneously,the control mice were injected with normal saline (NS group).All the groups were divided into subgroups,standard chow group (SC),and high-fat diet group (HF).ApoE-/- pregnant mice served as a control group.Systolic blood pressure (SBP),urine protein,and histopathologic changes of placenta and liver in all groups were observed and statistically analyzed.Results In WT and apoE-/- L-NAME subgroups,blood pressure and urine protein were significantly higher than those in all the gestational age matched NS groups (P ＜0.05).Compared to other groups,remarkable liver fatty infiltration and lipid storage in placenta were found in early- and mid-L-NAME subgroups in apoE-/- mice (P ＜0.05),especially in the early- and mid-HF+L-NAME subgroups in apoE-/- mice (P ＜0.05).More lipid storage droplets both in liver and placenta were found in ApoE-/- mice than that of WT groups (P ＜0.05).Morphology histopathologic examination of placentas showed varying degrees of fibrinoid necrosis and villous interstitial edema in early- and mid-L-NAME both in HF and SC of apoE-/- and WT subgroups compared to NS controls (P ＜0.05).But there was no significant difference between HF and SC subgroups (P＞0.05),and no difference between apoE-/-and WT groups (P＞0.05).Conclusions Preeclampsia-like conditions could be induced by L-NAME in mice at different gestational stages.Both WT and apoE-/- genotype mice with preeclampsia-like symptoms in early and mid stages of pregnancy presented lipid deposition in the placenta and hepatic fatty infiltration.To alter the environmental condition by feeding high-fat diet was harmful to the mother and the fetus.High-fat diet aggravated the impact of liver fatty infiltration at early and mid gestational stages especially in the apoE-/- mouse model.These results further revealed the association between early-onset preeclampsia and the dysoxidation of fatty acids.Chin Med J 2012; 125(19):3532-3538