Axl encodes the tyrosine-protein kinase receptor, participating in the proliferation and migration of many cells. This study examined the role of Axl in functions of endothelial progenitor cells (EPCs). Axl was detected by RT-PCR and Western blotting in both placentas and EPCs from normal pregnancy and preeclampsia patients. The Axl inhibitor, BMS777-607, was used to inhibit the Axl signalling pathway in EPCs. Cell proliferation, differentiation, migration and adhesion were measured by CCK-8 assay, cell differentiation assay, Transwell assay, and cell adhesion assay, respectively. Results showed the expression levels of Axl mRNA and protein were significantly higher in both placentas and EPCs from preeclampsia patients than from normal pregnancy (P<0.05). After treatment with BMS777-607, proliferation, differentiation, migration and adhesion capability of EPCs were all significantly decreased. Our study suggests Axl may play a role in the function of EPCs, thereby involving in the pathogenesis of preeclampsia.
Adult ; Aminopyridines ; pharmacology ; Blood Pressure ; Case-Control Studies ; Cell Adhesion ; drug effects ; Cell Differentiation ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Female ; Fetal Blood ; cytology ; enzymology ; Gene Expression Regulation ; Gestational Age ; Human Umbilical Vein Endothelial Cells ; drug effects ; enzymology ; pathology ; Humans ; Placenta ; metabolism ; physiopathology ; Pre-Eclampsia ; blood ; genetics ; physiopathology ; Pregnancy ; Primary Cell Culture ; Protein Kinase Inhibitors ; pharmacology ; Proto-Oncogene Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Pyridones ; pharmacology ; RNA, Messenger ; antagonists & inhibitors ; genetics ; metabolism ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; genetics ; metabolism ; Stem Cells ; drug effects ; enzymology ; pathology

BACKGROUNDPreeclampsia is a multifactorial disease during pregnancy. Dysregulated lipid metabolism may be related to some preeclampsia. We investigated the relationship between triglycerides (TGs) and liver injury in different preeclampsia-like mouse models and their potential common pathways.

METHODSPreeclampsia-like models (Nw-nitro-L-arginine-methyl ester [L-NAME], lipopolysaccharide [LPS], apolipoprotein C-III [Apo] transgnic mice + L-NAME, β2 glycoprotein I [βGPI]) were used in four experimental groups: L-NAME (LN), LPS, Apo-LN and βGPI, respectively, and controls received saline (LN-C, LPS-C, Apo-C, βGPI-C). The first three models were established in preimplantation (PI), early-, mid- and late-gestation (EG, MG and LG). βGPI and controls were injected before implantation. Mean arterial pressure (MAP), 24-hour urine protein, placental and fetal weight, serum TGs, total cholesterol (TC) and pathologic liver and trophocyte changes were assessed.

RESULTSMAP and proteinuria were significantly increased in the experimental groups. Placenta and fetal weight in PI, EP and MP subgroups were significantly lower than LP. Serum TGs significantly increased in most groups but controls. TC was not different between experimental and control groups. Spotty hepatic cell necrosis was observed in PI, EG, MG in LN, Apo-LN and βGPI, but no morphologic changes were observed in the LPS group. Similar trophoblastic mitochondrial damage was observed in every experimental group.

CONCLUSIONSEarlier preeclampsia onset causes a higher MAP and urine protein level, and more severe placental and fetal damage. Preeclampsia-like models generated by varied means lead to different changes in lipid metabolism and associated with liver injury. Trophoblastic mitochondrial damage may be the common terminal pathway in different preeclampsia-like models.

Animals ; Cholesterol ; blood ; Disease Models, Animal ; Female ; Fetal Weight ; physiology ; Liver ; injuries ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondrial Diseases ; blood ; pathology ; Placenta ; metabolism ; Pre-Eclampsia ; blood ; pathology ; Pregnancy ; Triglycerides ; blood ; Trophoblasts ; pathology

In order to assess the number and function of macrophages in the placenta of pregnancy complicated with gestational diabetes mellitus (GDM) as well as those of normal pregnancies, placenta samples were collected from 15 GDM patients (GDM group) and 10 normal pregnant women (control group). The expression levels of macrophage markers (CD68/CD14) and inflammatory cytokines (IL-6/TNF-α) in placenta were detected using immunohistochemistry and PCR. The results showed that the number of CD68+ or CD14+ cells in the GMD group was remarkably higher than that in the control group (P<0.05), indicating that the number of macrophages in the GDM group was significantly greater than that in the control group. The mRNA expression levels of CD68+, IL-6 and TNF-α were higher in the GMD group than in the control group. In conclusion, more macrophages accumulate in placenta of pregnancy complicated with GDM, and the expression levels of pro-inflammation factors are also increased in GDM pregnancies, suggesting that macrophages and inflammatory mediators (IL-6 and TNF-α) may play an important role in GDM.
Adult ; Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Cell Count ; Cytokines ; genetics ; immunology ; metabolism ; Diabetes, Gestational ; genetics ; immunology ; metabolism ; Female ; Humans ; Immunohistochemistry ; Inflammation Mediators ; immunology ; metabolism ; Interleukin-6 ; genetics ; immunology ; metabolism ; Lipopolysaccharide Receptors ; genetics ; metabolism ; Macrophages ; immunology ; metabolism ; pathology ; Placenta ; immunology ; metabolism ; Pregnancy ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; genetics ; immunology ; metabolism

Intrahepatic cholestasis of pregnancy (ICP) is an unique complication in pregnancy, which usually manifests in the second or third trimester, and mainly harms the fetus. Its pathogenesis is not yet clear, and placental pathological changes are insufficient to explain the clinical phenomenon.Recent studies had shown that the important cause of perinatal deaths may be the damage to the placental structure and function caused by the high bile acid level. In addition, the change of placental structure and function, umbilical cord factors, and endocrine changes can also cause the fetal development and intrauterine hypoxia. In recent years related researches focus on the toxic effect of bile acid on fetus heart, lungs, brain, liver, and other important organs, the placental vascular pathology, hemodynamic changes, umbilical cord blood vessel factors and the endocrine changes.
Bile Acids and Salts ; metabolism ; Cholestasis, Intrahepatic ; metabolism ; pathology ; Female ; Fetal Diseases ; etiology ; metabolism ; Fetus ; metabolism ; Humans ; Maternal-Fetal Exchange ; Placenta ; pathology ; Pregnancy ; Pregnancy Complications ; metabolism ; pathology ; Umbilical Cord ; metabolism ; pathology

OBJECTIVETo detect the expression profiles of suppressor of cytokine signaling 3 (SOCS3), interleukin (IL)-10, and tumor necrosis factor-alpha (TNF-a) in the placenta of women with intrahepatic cholestasis of pregnancy (ICP) and determine the clinical significance of the differential expressions.

METHODSPlacentas were collected from 37 ICP gravidas who delivered through cesarean section at the First Teaching Hospital of Xingjiang Medical University from October 2010 to May 2011 and from 35 healthy pregnant women (controls). SOCS3, TNF-a, and IL-10 protein levels were detected by immunoblotting and the Envision immunohistochemical method.

RESULTSTNF-a and IL-10 expression was detected in placentas of both groups, and was present mainly in the cytoplasm of trophoeytes. IL-10 expression was obviously lower in the ICP placentas than in the control placentas; meanwhile, TNF-a expression was obviously higher than in the control placentas (Z=-2.63, P less than 0.01). SOCS3 protein was significantly more abundant in the control placentas than in the ICP placentas. Furthermore, SOCS3 and IL-10 placental expressions were positively correlated (r=0.494, P less than 0.01), but there was a negative correlation between SOCS3 and TNF-a placental expressions (r=-0.472, P less than 0.01).

CONCLUSIONIn ICP, an increase of the type 1 cytokine, TNF-a, is associated with decreases of the type 2 cytokine, IL-10, and of SOCS3, which may reduce the secretion of IL-10. Furthermore, SOCS3 may contribute to ICP pathogenesis by modulating the Th1/Th2 cytokine balance.

Adult ; Case-Control Studies ; Cholestasis, Intrahepatic ; metabolism ; pathology ; Female ; Humans ; Interleukin-10 ; metabolism ; Placenta ; metabolism ; Pregnancy ; Pregnancy Complications ; metabolism ; pathology ; Pregnancy Trimester, Third ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Young Adult

Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration. Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placenta growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1, also known as Flt-1) and VEGF receptor 2 (VEGFR-2, also known as Flk-1 in mice and KDR in human) have a decisive role. In this review, we describe the discovery and molecular characteristics of PlGF, and discuss the biological role of this growth factor in physiological and pathological conditions.
Animals ; Endothelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Developmental ; Humans ; Mice ; Mice, Knockout ; Neovascularization, Pathologic/genetics ; Neovascularization, Physiologic/genetics ; Nitric Oxide/metabolism ; Placenta/*metabolism ; Pregnancy ; Pregnancy Proteins/genetics/*metabolism ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Vascular Endothelial Growth Factor A/metabolism

Antigens, CD34 ; metabolism ; Choriocarcinoma ; pathology ; Diagnosis, Differential ; Female ; Hemangioma ; metabolism ; pathology ; Humans ; Keratin-18 ; metabolism ; Mesenchymoma ; pathology ; Placenta ; pathology ; Placenta Diseases ; metabolism ; pathology ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Pregnancy ; Pregnancy Complications, Neoplastic ; metabolism ; pathology ; Young Adult

OBJECTIVETo investigate the anti-apoptotic effect of low molecular weight heparin (LMWH) in the placenta of rats with preeclampsia-like symptoms.

METHODSThirty pregnant Wistar rats were randomized equally into 3 groups and received subcutaneous saline injection (control group), 200 mg/kg L-NAME injection to induce preeclampsia symptoms (PE group), or L-NAME with 40 µl/kg LMWH injections (LMWH group). The blood pressure, urine protein, the number of pups and the weight of the fetuses and placenta were measured, and the placental apoptotic index was measured by TUNEL assay. The expression of cleaved caspase-3, Bcl-2 and Bax in the placenta were examined by Western blotting.

RESULTSCompared with the control group, L-NAME injections caused significantly increased blood pressure and urine protein (P<0.05), which were significantly lowered by LWMH (P<0.05). The number and weight of normal pups were significantly lower in PE group than in the control group (P<0.05) and LMWH group (P<0.05); in LMWH group, the weight of pups was still lower than that of the control group (P<0.05) but the number of normal pups was comparable (P>0.05). The LMWH group showed a significantly lower placental apoptosis index than the PE group (P<0.05) with also significantly lower cleaved caspase-3 and Bax and higher Bcl-2 expressions (P<0.05). The apoptosis index and expressions of cleaved caspase-3, Bcl-2 and Bax protein were similar between LMWH group and normal pregnant group (P>0.05).

CONCLUSIONLMWH can alleviate preeclampsia-like symptoms and decrease the apoptosis in the placenta of rats possibly by enhancing Bcl-2 and suppressing Bax expressions.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Female ; Heparin, Low-Molecular-Weight ; pharmacology ; Placenta ; cytology ; Pre-Eclampsia ; pathology ; Pregnancy ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein ; metabolism

Twin pregnancy with mosaic partial hydatidiform mole (PHM) and survival of two healthy fetuses following in vitro fertilization and embryos transfer (IVF-ET) is a rare situation and is considered a challenge for management. A 32-year-old Chinese woman conceived twin pregnancy following IVF-ET. At 22 weeks' gestation, an additional intrauterine echogenic mass with features of PHM were shown by successive ultrasound examinations. At 35 weeks' gestation, two live male infants and two placentas were delivered by caesarean section (CS). Histologic examination of the abnormal placenta confirmed mosaic PHM. Genetic study showed the abnormal placental mosaicism (expressed in molar-69XXY and normal vili-46XY), co-existing with a hypospadia new-born (46XY) in one amniotic sac. However, the other one was normal. Serial serum β-hCG levels showed a declining trend and serum β-human chorionic gonadotropin (hCG) were undetectable at 6 months after delivery. The case demonstrated that it is possible to prolonged gestation by PHM under close surveillance during the entire pregnancy.
Adult ; Female ; Fertilization in Vitro ; Humans ; Hydatidiform Mole ; genetics ; Infant, Newborn ; Male ; Mosaicism ; Placenta ; metabolism ; pathology ; Pregnancy ; Pregnancy, Twin ; genetics

OBJECTIVETo investigate the roles of MMPs-9, TIMP-1 and TIMP-2 in cesarean section scar healing.

METHODSThe expressions of the MMPs-9, TIMP-1 and TIMP-2 were detected by EnVision immunohistochemistry in 22 pregnant women with serious complications of the uterine scar, including 8 with early caesarean scar pregnancy (CSP) and 14 with full-term pregnancy undergoing hysterectomy for placenta previa or implanted placenta. Thirty-eight full-term pregnant women without serious complications of the uterine scar and 32 normal full-term pregnant women served as the control I and control II groups, respectively.

RESULTSThe expressions of MMPs-9 and TIMP-1 differed significantly between the 3 groups (P<0.05), whereas TIMP-2 did not (P>0.05). Spearman rank correlation analysis showed that the expression of MMPs-9 in the uterine scar tissues was positively correlated with poor uterine scar healing with the correlation coefficients of 0.309 and 0.643. An increased severity of poor healing scar was associated with a significantly increased expression of MMPs-9 (P<0.05).

CONCLUSIONThe imbalanced expressions of MMPs-9 and TIMP-1 in injury repair can be related to poor uterine scar healing and CSP.

Adult ; Cesarean Section ; adverse effects ; Cicatrix ; etiology ; metabolism ; Female ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Placenta Previa ; surgery ; Pregnancy ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Uterus ; pathology ; Wound Healing ; Young Adult