ObjectiveTo assess associations of elevated lipid levels during gestation with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM).MethodsThis prospective cohort study was conducted in a tertiary maternal hospital in Shanghai, China from February to November 2014. Lipid constituents, including triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) of 1310 eligible women were assessed in the first (10–13+ weeks), second (22–28 weeks) and third (30–35 weeks) trimesters consecutively. Associations of lipid profiles with HDP and/or GDM outcomes were assessed.ResultsCompared with the normal group, maternal TG concentrations were higher in the HDP/GDM groups across the three trimesters (p<0.001); TC and LDL-c amounts were only higher in the first trimester for the HDP and GDM groups (p<0.05). HDL-c levels were similar in the three groups. Compared with intermediate TG levels (25–75th centile), higher TG amounts (>75th centile) were associated with increased risk of HDP/GDM in each trimester with aORs (95% CI) of 2.04 (1.41 to 2.95), 1.81 (1.25 to 2.63) and 1.78 (1.24 to 2.54), respectively. High TG elevation from the first to third trimesters (>75th centile) was associated with increased risk of HDP, with an aOR of 2.09 (1.16 to 3.78). High TG elevation before 28 weeks was associated with increased risk of GDM, with an aOR of 1.67 (1.10 to 2.54). TG elevation was positively correlated with weight gain during gestation (R=0.089, p=0.005).ConclusionsControlling weight gain during pregnancy could decrease TG elevation and reduce the risk of HDP/GDM. TGs could be used as follow-up parameters during complicated pregnancy, while other lipids are meaningful only in the first trimester.

Preeclampsia is a common pregnancy-specific disorder characterized by elevated blood pressure and proteinuria. Activation of the maternal immune system and impaired placental angiogenesis are thought to contribute to the pathogenesis of preeclampsia. TLR9 (Toll-like receptor 9) plays a role in innate immunity, defending the organism against infection. The purpose of this study was to determine whether TLR9 inhibits angiogenesis at the fetomaternal interface under conditions of preeclampsia. We confirmed the downregulation of VEGFA (vascular endothelial growth factor A) and upregulation of TLR9 and sFLT1 (soluble vascular endothelial growth factor receptor 1) in placentas from preeclamptic women. Then, we established a mouse model with preeclampsia-like symptoms using the synthetic TLR9 agonist CpG (cytidine-phosphate-guanosine)-ODN (oligodeoxynucleotide; ODN1826). We observed the downregulation of VEGFA and the upregulation of sFLT1 in placentas from the preeclampsia-like animal model and in trophoblasts treated with CpG-ODN (ODN2006). In addition, silencing TLR9 promoted the migration and invasion of HTR8/SVneo cells. In conclusion, TLR9 is capable of robustly suppressing angiogenesis by differentially regulating the expression of VEGFA and sFLT1 at the fetomaternal interface, potentially contributing to the development of preeclampsia.

Epithelial ovarian cancer (EOC) is the most lethal tumor of all gynecologic tumors. There is no curative therapy for EOC thus far. The tumor-homing ability of adult mesenchymal stem cells (MSCs) provide the promising potential to use them as vehicles to transport therapeutic agents to the site of tumor. Meanwhile, studies have showed the intrinsic anti-tumor properties of MSCs against various kinds of cancer, including epithelial ovarian cancer. Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a novel source for adult MSCs and exert restorative function in some diseases. Whether EnSCs endow innate anti-tumor properties on EOC cells has never been reported. By using tumor-bearing animal model and ex vivo experiments, we found that EnSCs attenuated tumor growth by inducing cell cycle arrest, promoting apoptosis, disturbing mitochondria membrane potential and decreasing pro-angiogenic ability in EOC cells in vitro and/or in vivo. Furthermore, EnSCs decreased AKT phosphorylation and promoted nuclear translocation of Forkhead box O-3a (FoxO3a) in EOC cells. Collectively, our findings elucidated the potential intrinsic anti-tumor properties of EnSCs on EOC cells in vivo and in vitro. This research provides a potential strategy for EnSC-based anti-cancer therapy against epithelial ovarian cancer.