Expression may play an important role in some patients with early-onset PE. Yet not all patients with PE have FAO disorders. Previously, we found no significant difference in LCHAD protein expression between late-onset PE and controls [2]. No change in triglycerides (TG) level was found in a PE-like mouse model of reduced uterine perfusion pressure [13]. Therefore, different onset times and different subtypes of PE may exhibit different FAO disorders. The mechanism about how FAO disorders result in PE is unclear. FAO disorders can cause serum FFA increase and high FFA level will activate oxidative stress response. There have been many researches about the effects of oxidative stress on endothelial injury in the pathogenesis of preeclampsia. Reactive oxygen species generated during oxidative stress attack the phospholipids of cell membranes and react with polyunsaturated fatty acids to form lipid peroxides resulting in cellular injury [14]. So we speculate that abnormal FAO may induce PE through oxidative stress pathway. In the present study, we established classical PE-like models by L-NA and lipopolysaccharide (LPS) injection and used ApoC3 transgenic mice with abnormal fatty acid metabolism and an APS mouse model with underlying maternal disease to establish PE-likemodels induced by different factors. Also we chose two time points, pre-implantation and mid-gestation, to establish PE-like models induced by different times. Mid-gestation is classical time to establish PE models. We chose pre-implantation time to investigate the effects of adverse factors on the placenta before it began to form. We used this multifactorial and different time research platform to investigate the role of LCHAD and its relationship with oxidative stress in the pathogenesis of different subtypes of PE.Materials and Methods Ethics StatementThe animal experiment was approved by the Animal Care Committee and Medical Ethics Committee of Peking University (permit number: LA2012-8) and procedures were conducted according to its guidelines. All surgery was performed under anesthesia, and all efforts were made to minimize suffering.Establishment and identification of animal modelsC57BL/6J mice were from the Department of Laboratory Animal Science, Peking University, and C57BL/6J mice with transgenic overexpression of apoC3 were supported by the Institute of Cardiovascular Sciences, Peking University HealthPLOS ONE | www.plosone.orgFatty Acid Oxidation in Different Preeclampsia-Like ModelsFetal weight (g)0.6360.07a0.7160.08a0.8260.0.8060.Pre0.7160.06a0.6760.Science Center. We housed 8- to 10-week-old virgin female and 10- to 14-week-old male mice under controlled conditions and fed them standard mouse chow with water available ad libitum.CMK The mice were mated at a ratio of 2:1 females to males and females were inspected daily for vaginal plugs, designated as day 1 of pregnancy.Ketoconazole Mice were randomly divided into control, ApoC3+NS, ApoC3+ L-NA, L-NA, LPS and b2GPI groups.PMID:23563799 Except for the b2GPI group, the other groups were subdivided into pre-implantation (Pre) and mid-gestation (Mid) subgroups according to injection time (n = 10 per group). Transgenic mice in ApoC3+L-NA and wild-type mice in L-NA group received a daily subcutaneous injection with L-NA (Sigma, USA), 50 mg/kg/d, [15,16] from day 3 (Pre) or 11 (Mid) to day 17 of pregnancy. For LPS mice, wildtype mice received a single injection with an ultra-low dose of LPS (1 mg/kg body weight, Sigma) on day 3 or 11 of preg.