Possible Association between Cathepsin V and the Development of Placenta Accreta Spectrum Disorders.

BACKGROUND/AIMS: The study aimed to evaluate molecular changes related to trophoblast adhesion in placenta accreta spectrum (PAS) disorders. METHODS: A retrospective analysis of 10 PAS cases in which both the trophoblast adherent site and the non-adherent site were identified was performed in April 2010 and March 2013. Microarray analysis and reverse transcription polymerase chain reaction (RT-PCR) analyses were performed to extract upregulated genes in the adherent site. Gene expression changes were examined by immunohistochemistry. RESULTS: Microarray analysis showed that 157 transcripts were > 3-fold upregulated, including the following: a disintegrin and metalloproteinase-28 (ADAM28), 3.10-fold; cathepsin V (CTSV), 3.73-fold; cathepsin S (CTSS), 3.46-fold; and matrix metalloproteinase-19 (MMP19), 3.41-fold. RT-PCR showed relatively high mRNA expressions. On immunohistochemistry, extravillous trophoblast (EVT) at the non-adherent site showed weak or no CTSV expression, whereas EVT that invaded myometrium at the adherent site showed strong expression (histological score, median [min-max], 115.6 [37.6-153.6] vs. 184.8 [56.4-222.8], p < 0.05). MMP19 showed moderate staining, with no difference between the adherent and non-adherent sites. ADAM28 and CTSS showed weak or no staining. DISCUSSION: This limited study suggests that CTSV may be involved in the pathogenesis of PAS.

Molecular hydrogen ameliorates several characteristics of preeclampsia in the Reduced Uterine Perfusion Pressure (RUPP) rat model.

Oxidative stress plays an important role in the pathogenesis of preeclampsia. Recently, molecular hydrogen (H2) has been shown to have therapeutic potential in various oxidative stress-related diseases. The aim of this study is to investigate the effect of H2 on preeclampsia. We used the reduced utero-placental perfusion pressure (RUPP) rat model, which has been widely used as a model of preeclampsia. H2 water (HW) was administered orally ad libitum in RUPP rats from gestational day (GD) 12-19, starting 2 days before RUPP procedure. On GD19, mean arterial pressure (MAP) was measured, and samples were collected. Maternal administration of HW significantly decreased MAP, and increased fetal and placental weight in RUPP rats. The increased levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and diacron reactive oxygen metabolites as a biomarker of reactive oxygen species in maternal blood were decreased by HW administration. However, vascular endothelial growth factor level in maternal blood was increased by HW administration. Proteinuria, and histological findings in kidney were improved by HW administration. In addition, the effects of H2 on placental villi were examined by using a trophoblast cell line (BeWo) and villous explants from the placental tissue of women with or without preeclampsia. H2 significantly attenuated hydrogen peroxide-induced sFlt-1 expression, but could not reduce the expression induced by hypoxia in BeWo cells. H2 significantly attenuated sFlt-1 expression in villous explants from women with preeclampsia, but not affected them from normotensive pregnancy. The prophylactic administration of H2 attenuated placental ischemia-induced hypertension, angiogenic imbalance, and oxidative stress. These results support the theory that H2 has a potential benefit in the prevention of preeclampsia.

Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ-114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague-Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p < 0.01), increased lung volume (p < 0.01), improved alveolarization and pulmonary artery remodeling using histological analysis, and improved respiratory function using gasometric analysis (pH; p < 0.05, and PCO2 ; p < 0.01). In addition, antenatal Saireito significantly decreased endothelin-1 and endothelin receptor A expression in the pulmonary arteries. Taken together, our results demonstrated that antenatal Saireito can improve fetal pulmonary hypoplasia and pulmonary vascular remodeling and, as a result, can improve respiratory function in a rat CDH model. Copyright © 2016 John Wiley & Sons, Ltd.

Efficacy and safety of daikenchuto (TJ-100) in pregnant women with constipation.

OBJECTIVE: Constipation is common and a significant problem in pregnant women. The purpose of this study was to examine the efficacy and the safety of daikenchuto in pregnant women with constipation. MATERIAL AND METHODS: This was a prospective study, and a total of 20 patients were registered between February 2010 and August 2012. The patients received 7.5 g/d of daikenchuto for 28 days from the day of registration. All enrolled patients were asked to complete the constipation assessment scale (CAS) every day. In addition, we measured the aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine levels to assess the adverse effects of daikenchuto. RESULTS: The CAS scores were significantly lower at 28 days after daikenchuto treatment (p = 0.019), with a significant effect achieved on Day 1. The impact of the therapy was greatest in the second trimester (p = 0.043). No significant adverse effects of daikenchuto were observed, and the rates of preterm birth and pregnancy-induced hypertension were 10% and 5%, respectively, which are similar to previously reported values. CONCLUSION: We herein demonstrated the efficacy and safety of daikenchuto in pregnant women with constipation. We hope that our findings will aid in the management of constipation in pregnant women.

Relationship between the cortisol levels in umbilical cord blood and neonatal RDS/TTN in twin pregnancies.

OBJECTIVE: Twin neonates have a higher risk of respiratory complications, such as respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), than singleton neonates. The purpose of this study was to evaluate the relationship between the cortisol levels in the umbilical cord and neonatal RDS/TTN in twin pregnancies. METHODS: We analyzed data obtained from 106 neonates (53 twin pairs), comprising 33 dichorionic twin (DCT) and 20 monochorionic twin (MCT) gestations. All infants were delivered via scheduled cesarean section without labor. We measured the cortisol levels in umbilical vein blood using enzyme-linked immunosorbent assay. RESULTS: The cortisol levels in the umbilical vein were significantly lower in the RDS/TTN group than in the no RDS/TTN group (p = 0.004). The umbilical cortisol levels in the TTN group were between the values observed in the RDS group and no RDS/TTN group. We subsequently analyzed the cut-off cortisol values for RDS/TTN and observed higher accuracy in the DCTs than in the MCTs. CONCLUSIONS: Neonates who develop RDS/TTN have significantly lower cortisol levels in the umbilical cord at birth than no RDS/TTN neonates in twin pregnancies. When applying these data in clinical practice, physicians should pay attention to differences based on chorionicity.

Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia.

Exposure to inflammation in utero is related to perinatal brain injury, which is itself associated with high rates of long-term morbidity and mortality in children. Novel therapeutic interventions during the perinatal period are required to prevent inflammation, but its pathogenesis is incompletely understood. Activated microglia are known to play a central role in brain injury by producing a variety of pro-inflammatory cytokines and releasing oxidative products. The study is aimed to investigate the preventative potential of molecular hydrogen (H2), which is an antioxidant and anti-inflammatory agent without mutagenicity. Pregnant ICR mice were injected with lipopolysaccharide (LPS) intraperitoneally on embryonic day 17 to create a model of perinatal brain injury caused by prenatal inflammation. In this model, the effect of maternal administration of hydrogen water (HW) on pups was also evaluated. The levels of pro-inflammatory cytokines, oxidative damage and activation of microglia were determined in the fetal brains. H2 reduced the LPS-induced expression of pro-inflammatory cytokines, oxidative damage and microglial activation in the fetal brains. Next, we investigated how H2 contributes to neuroprotection, focusing on microglia, using primary cultured microglia and neurons. H2 prevented LPS- or cytokine-induced generation of reactive oxidative species by microglia and reduced LPS-induced microglial neurotoxicity. Finally, we identified several molecules influenced by H2, involved in the process of activating microglia. These results suggested that H2 holds promise for the prevention of inflammation related to perinatal brain injury.

Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury.

Fetal brain injury is often related to prenatal inflammation; however, there is a lack of effective therapy. Recently, molecular hydrogen (H2), a specific antioxidant to hydroxyl radical and peroxynitrite, has been reported to have anti-inflammatory properties. The aim of this study was to investigate whether maternal H2 administration could protect the fetal brain against inflammation. Pregnant C3H/HeN mice received an intraperitoneal injection of lipopolysaccharide (LPS) on gestational day 15.5 and were provided with H2 water for 24 h prior to LPS injection. Pup brain samples were collected on gestational day 16.5, and the levels of apoptosis and oxidative damage were evaluated using immunohistochemistry. Interleukin-6 (IL-6) levels were examined using real-time PCR. The levels of apoptosis and oxidative damage, as well as the levels of IL-6 mRNA, increased significantly when the mother was injected with LPS than that in the control group. However, these levels were significantly reduced when H2 was administered prior to the LPS-injection. Our results suggest that LPS-induced apoptosis, oxidative damage and inflammation in the fetal brain were ameliorated by maternal H2 administration. Antenatal H2 administration might protect the premature brain against maternal inflammation.

Risk assessment for neonatal RDS/TTN using gestational age and the amniotic lamellar body count in twin pregnancies.

BACKGROUND: The amniotic lamellar body count (LBC) is useful for predicting respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN) in twin pregnancies. However, the risk of neonatal respiratory complications varies with gestational age (GA). We herein created a model to predict the risk for RDS and TTN using GA and the LBC in twin pregnancies. METHODS: Six hundred thirty-two amniotic fluid samples, comprising 169 dichorionic twin (DCT) and 147 monochorionic twin (MCT) gestations, were obtained at Cesarean section. The samples were analyzed immediately without centrifugation. A logistic regression model including the LBC and GA was used to develop the prediction model for RDS/TTN. RESULTS: There were 101 neonates (16.0%) with RDS/TTN. The GA and LBC were significant independent factors affecting RDS/TTN. According to the logistic regression model, we determined the probability of RDS/TTN given the values of GA and the LBC. The overall diagnostic accuracy for predicting neonatal RDS/TTN using GA and the LBC was higher than the use of the LBC alone. CONCLUSIONS: GA-specific LBC cutoffs for the risk assessment of neonatal RDS/TTN have been considered to be more accurate in twin pregnancies. Our findings provide valuable, new information for the management of twin pregnancies.

Is the serum l-arginine level during early pregnancy a predictor of pregnancy-induced hypertension?

The objective of this study was to determine the concentration of serum l-arginine in healthy pregnant women and infant cord blood and to compare them with those in patients with pregnancy-induced hypertension (PIH). The serum concentration of l-arginine in normal pregnant women at early gestation (n = 186) was determined and analyzed based on maternal factors such as the age, pre-pregnancy body mass index (BMI), smoking and alcohol habits before pregnancy. Similarly, the concentration of cord blood of the newborns (n = 142) was also analyzed. These values were compared with those in the PIH group (n = 21). The potential risk factors for PIH were also estimated. The serum concentration of l-arginine at early gestation in normal pregnant women (88.65 ± 19.96 µM) was not affected by the maternal age and BMI before pregnancy. A lower l-arginine concentration at early gestation (<70 µM) significantly elevated PIH risk [adjusted odds ratio (OR) = 4.26, 95% CI 1.29-14.50]. In addition, either women with large body mass before pregnancy (BMI>25 kg/m(2)) or primipara women also showed a significant association with PIH risk [adjusted OR = 10.55 (2.95-40.68); 5.25 (1.72-19.15), respectively]. In conclusion, a lower l-arginine concentration at early gestation, overweight before pregnancy (BMI>25 kg/m(2)) and primipara could predict to the development of PIH.

Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders.

Amniotic fluid contains numerous biomolecules derived from fetus and mother, thus providing precious information on pregnancy. Here, we evaluated oxidative stress of human amniotic fluid and measured the concentration of catalytic Fe(II). Amniotic fluid samples were collected with consent from a total of 89 subjects in Nagoya University Hospital, under necessary medical interventions: normal pregnancy at term, normal pregnancy at the 2nd trimester, preterm delivery with maternal disorders but without fetal disorders, congenital diaphragmatic hernia, fetal growth restriction, pregnancy-induced hypertension, gestational diabetes mellitus, Down syndrome and trisomy 18. Catalytic Fe(II) and oxidative stress markers (8-hydroxy-2'-deoxyguanosine, 8-OHdG; dityrosine) were determined with RhoNox-1 and specific antibodies, respectively, using plate assays. Levels of 8-OHdG and dityrosine were higher in the 3rd trimester compared with the 2nd trimester in normal subjects, and the abnormal groups generally showed lower levels than the controls, thus suggesting that they represent fetal metabolic activities. In contrast, catalytic Fe(II) was higher in the 2nd trimester than the 3rd trimester in the normal subjects, and overall the abnormal groups showed higher levels than the controls, suggesting that high catalytic Fe(II) at late gestation reflects fetal pathologic alterations. Notably, products of H2O2 and catalytic Fe(II) remained almost constant in amniotic fluid.

Amniotic lamellar body count: predicting and distinguishing neonatal respiratory complications in twin pregnancies.

BACKGROUND: Twin pregnancies have a higher rate of preterm births, making precise prediction of neonatal respiratory disorders essential. We herein examined the amniotic lamellar body count (LBC) and found it to be an accurate predictor of respiratory disorders in twin pregnancies. METHODS: Five hundred fourteen amniotic fluid samples, comprising 132 dichorionic twin (DCT) and 125 monochorionic twin (MCT) gestations, were obtained at cesarean section performed at 29 to 38 gestational weeks. Samples were analyzed immediately without centrifugation. RESULTS: There were 26 neonates (5.1%) with respiratory distress syndrome (RDS) and 43 (8.4%) with transient tachypnea of the newborn (TTN). The LBC in neonates with TTN (5.12×10(4)/µl) was between the counts in RDS (1.26×10(4)/µl) and controls (10.6×10(4)/µl), which differed significantly. Twin concordance rates were significantly higher for TTN in MCT gestations than DCT gestations (p=0.003) and delta LBC value was significantly smaller in MCT (3.15±0.4×10(4)/µl) than DCT (5.17±0.5×10(4)/µl) gestations (p=0.003). CONCLUSIONS: The amniotic LBC is useful for predicting respiratory disorders, including RDS and TTN, in twin pregnancies. The data in this study may indicate a genetic predisposition to TTN among MCTs.

Impact of warning bleeding on the cortisol level in the fetus and neonatal RDS/TTN in cases of placenta previa.

OBJECTIVE: The purpose of this study was to examine the levels of hormones in umbilical vein blood that affect the neonatal respiratory function in cases of placenta previa and to evaluate the impact of warning bleeding on the hormone levels and neonatal respiratory outcomes such as respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN). METHODS: We analyzed data obtained from 33 placenta previa cases without fetal or maternal complications at 36-38 weeks of gestation. We measured the levels of hormones such as cortisol, arginine vasopressin, epinephrine and norepinephrine in umbilical vein blood using ELISA. RESULTS: Warning bleeding was found to be a significant factor protecting against neonatal RDS/TTN (p = 0.049). The cortisol levels in the umbilical vein were significantly higher in the cases of previa with warning bleeding than in those without warning bleeding (p = 0.020) and significantly higher in the no RDS/TTN cases than in the RDS/TTN cases (p = 0.040). CONCLUSIONS: Warning bleeding increases the cortisol level in cases of placenta previa. We suggest that genital bleeding may induce stress for both the mother and fetus, resulting in increased cortisol production, thus functioning as a protective factor against neonatal respiratory disorders.

Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion.

Molecular hydrogen (H2) scavenges hydroxyl radicals. Recently, H2 has been reported to prevent a variety of diseases associated with oxidative stress in model systems and in humans. Here, we studied the effects of H2 on rat fetal hippocampal damage caused by ischemia and reperfusion (IR) on day 16 of pregnancy with the transient occlusion of the bilateral utero-ovarian arteries. Starting 2 days before the operation, we provided the mothers with hydrogen-saturated water ad libitum until vaginal delivery. We observed a significant increase in the concentration of H2 in the placenta after the oral administration of hydrogen-saturated water to the mothers, with less placental oxidative damage after IR in the presence of H2. Neonatal growth retardation was observed in the IR group, which was alleviated by the H2 administration. We analyzed the neuronal cell damage in the CA1 and CA3 areas of the hippocampus at day 7 after birth by immunohistochemical analysis of the 8-oxo-7,8-dihydro-2׳-deoxyguanosine- and 4-hydroxy-2-nonenal-modified proteins. Both oxidative stress markers were significantly increased in the IR group, which was again ameliorated by the H2 intake. Last, 8-week-old rats were subjected to a Morris water maze test. Maternal H2 administration improved the reference memory of the offspring to the sham level after IR injury during pregnancy. Overall, the present results support the idea that maternal H2 intake helps prevent the hippocampal impairment of offspring induced by IR during pregnancy.

Effect of placenta previa on neonatal respiratory disorders and amniotic lamellar body counts at 36-38weeks of gestation.

BACKGROUND: Pregnancies with placenta previa are significantly associated with preterm delivery and cesarean section. Therefore particular attention should be paid to the incidence of neonatal respiratory disorders in pregnancies with placenta previa. AIMS: The purpose of this study is to examine the relationship between placenta previa and neonatal respiratory disorders, including respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), and to evaluate the impact of placenta previa on the amniotic lamellar body count (LBC) values. METHODS: We analyzed the data from 186 registered elective cesarean cases without fetal or maternal complications at 36-38weeks of gestation. Amniotic fluid samples were analyzed immediately without centrifugation, and the LBC was measured using a platelet channel on the Sysmex XE-2100. RESULTS: RDS was present in four neonates (2.2%) and TTN in 12 neonates (6.5%). The rate of TTN was significantly higher and the LBC values were significantly lower in the placenta previa group than in the control group (P=0.002 and P=0.024). The adjusted odds ratio for neonatal TTN was 7.20 (95% confidence interval: 6.58-7.88) among females with placenta previa. In placenta previa, warning bleeding was a significant factor protecting against neonatal respiratory disorders (P=0.046). CONCLUSIONS: Placenta previa in itself is a risk factor for neonatal TTN. When an elective cesarean section is performed in cases with uncomplicated placenta previa, special care should be taken to monitor for neonatal TTN even at 36-38weeks of gestation.

Altered expression of enzymes regulating the activity of endothelin-1 in the lower segment of the human amnion during labor.

The level of endothelin (ET)-1, a uterotonin, increases in amniotic fluid during labor. The known metallopeptidases include ET-converting enzyme (ECE), which converts inactive precursor to potent ET-1, and neutral endopeptidase (NEP), which inactivates ET-1. These enzymes are present in fetal membranes, and the aims of this study were to establish the protein expression of the enzymes within the amnion of human fetal membranes. Expressions were compared between amnions obtained before and after term labor using a Western blot analysis and enzyme-linked immunosorbent assay, respectively. The localization of these enzymes was determined using immunohistochemistry. The protein expression of the enzymes and output of bioactive ET-1 in human amnion epithelial cells (HAECs) and mesenchymal cells (HAMCs) were investigated with and without proinflammatory cytokines, oxytocin, and prostaglandin treatment. The effects of sphingosine-1-phosphate (S1P), a bioactive lipid, were also examined. The protein expression of ECE-1 was significantly increased (P < 0.01), whereas that of NEP was significantly decreased, followed by increased ET-1 (P < 0.01), in the amnion obtained after labor (P < 0.01). HAECs and HAMCs primarily expressed ECE-1 and NEP, respectively. The protein expression of ECE-1 was significantly induced (P < 0.01). However, the NEP levels were significantly reduced (P < 0.05) by treatment with TNFalpha and IL1beta followed by the 7.5-fold and 6.5-fold increase of ET-1 (P < 0.01), respectively, in the HAECs. ET-1 was increased 2-fold by S1P (P < 0.01). These results suggest that the altered expression of enzymes regulating the activity of ET-1 during parturition is controlled by inflammatory cytokines.

The expression and characterization of endoglin in uterine leiomyosarcoma.

Endoglin (CD105), an accessory receptor of transforming growth factor-ß, is expressed in vascular endothelial cells. Recently, it was reported that endoglin expression was significantly associated with poorer survival in several cancers. In this study, we evaluated the role of endoglin in uterine leiomyosarcoma. We examined the expression of endoglin in 22 uterine leiomyosarcomas and the association between their expression and the outcome. Additionally, to evaluate the function of endoglin, we used SKN cells, a human uterine leiomyosarcoma cell line. We generated SKN cells stably transfected with plasmids encompassing shRNA targeting endoglin (shEng cells), and compared the ability of proliferation, migration, and invasion to control shRNA-transfected cells (shCon cells). We compared the level of VEGF and matrix metalloproteinases (MMP) in culture supernatants of shEndoglin and shControl cells. Nine patients were endoglin-positive and 13 patients were -negative. The endoglin-positive group had a significantly poorer overall survival and progression-free survival than the endoglin-negative group. In an in vitro study, there was no difference in cell proliferation between shEng and shCon cells. On the other hand, shEng cells showed a lower ability for migration and invasion than shControl cells. The activity of MMP-9 and VEGF level in the supernatant from shEng cells were lower than in shCon cells. In uterine leiomyosarcoma, endoglin expression was associated with a poor prognosis. It was suggested that endoglin up-regulated invasion and VEGF secretion. The investigation of endoglin may lead to a new strategy in uterine leiomyosarcoma therapy.

Amniotic lamellar body count and congenital diaphragmatic hernia in humans and in a rat model.

BACKGROUND: We examined the extent of fetal lung hypoplasia and lung maturation using the amniotic lamellar body count (LBC) in congenital diaphragmatic hernia (CDH). METHODS: We obtained 30 amniotic fluid samples from human CDH cases during cesarean section. We assessed LBC, magnetic resonance imaging (MRI), and ultrasound findings for predicting the prognosis of CDH. We collected newborn amniotic fluid and lung tissue at embryonic day (E)21 from normal and nitrofen-induced CDH rats (administered 100 mg orally at E9). Amniotic LBCs in rats were measured using light microscopy. RESULTS: In human CDH, LBC was significantly higher in the surviving than in the deceased group (P < 0.01). A significant positive correlation was observed between LBC and percentage of fetal lung volume on MRI (P < 0.001; r = 0.716). In rats, LBC was significantly higher in controls than in CDH rats (P < 0.01) and correlated with fetal lung weight. CONCLUSION: We conclude that LBC is useful for predicting lung hypoplasia in human CDH after 35 gestational weeks and in a rat model of nitrofen-induced CDH.

Mucinous cystic neoplasm of the pancreas with severe dysplasia during pregnancy: case report and review of the literature.

OBJECTIVE: Mucinous cystic neoplasm (MCN) of the pancreas occurs mainly in women aged 40-60 years, so it is extremely rare in pregnant woman. CASE REPORT: A 28-year-old woman in the ninth week of pregnancy was referred to our hospital due to a tumor of the abdominal cavity. Abdominal ultrasound demonstrated a huge multicystic lesion in the left upper abdomen. There are mural nodules and hypertrophic septa partially with the presence of blood flow inside the tumor. Endoscopic ultrasonography was performed and a diagnosis of possible pancreatic MCN was made. At the second trimester, distal pancreatectomy with splenectomy was performed. Histopathological analysis of the specimen revealed a pancreatic MCN with severe dysplasia. Immunohistochemically, the tumor was positive for both progesterone and estrogen receptors in the stromal cell nuclei; moreover, MIB-1 stained positive in 10-20% of the nuclei in the epithelium with severe dysplasia. CONCLUSION: MCN carries malignant potential, therefore, early detection and complete surgery is recommended. MCN in pregnancy is rare and the abdomen is distended during pregnancy, so clinicians can easily miss the presence of the tumor. We should recognize the presence of MCN in pregnant woman. We speculate that the presence of blood flow within the tumor and MIB-1-positive cells can be a predictor for premalignant or malignant MCN.

The loss of endoglin promotes the invasion of extravillous trophoblasts.

Endoglin is a coreceptor for TGF-ß, which is expressed in syncytiotrophoblasts. The soluble form of endoglin (sEng) has been observed to increase in the serum of preeclamptic patients. Several studies have shown that endoglin is involved in cancer invasion. However, the role of endoglin in extravillous trophoblasts (EVT), which have an invasive phenotype, remains unknown. The present study was designed to investigate the expression and role of endoglin in human EVT. We found that endoglin was mainly expressed on cytotrophoblasts within the cell column during the first trimester and its expression decreased in the EVT by immunohistochemistry and immunocytochemistry. The expression of endoglin significantly increased after treatment with TGF-ß1 and TGF-ß3 in the human EVT cell line, HTR-8/SVneo, as detected by semiquantitative RT-PCR. To investigate the role of endoglin in EVT, the stable knockdown of endoglin was performed by lentiviral short hairpin RNA transfection into the HTR-8/SVneo cells. Although proliferation was not affected, the motility and invasiveness of the HTR-8/SVneo cells significantly increased by the knockdown of endoglin. Both the mRNA expression and secretion of urokinase-type plasminogen activator significantly increased in endoglin knockdown cells. The secretion of sEng was very low in HTR-8/SVneo, and the treatment of endoglin knockdown cells with 10 ng/ml sEng had no effect on their invasiveness. Therefore, the suppression of sEng was not involved in the increased invasiveness of endoglin knockdown cells. These results suggested that EVT increased their invasive function as a result of decreasing expression of transmembrane endoglin.

Maternal mental disorders and pregnancy outcomes: a clinical study in a Japanese population.

AIM: To assess the maternal and neonatal outcomes of pregnant women with mental disorders in Japan. MATERIAL AND METHODS: We conducted this retrospective cohort study to examine the patients who delivered at Nagoya University Hospital (2005-2009). Thereafter, the patients without any complications other than mental disorders and with several sources of psychiatric information were included in the present series, and the maternal and neonatal outcomes between patients with or without maternal mental disorders were compared. The psychiatric outcomes and the adverse effects of psychotropic drugs were also examined. RESULTS: A total of 1649 women delivered during this period, and 63 of them were complicated by maternal mental disorders. After the selection of patients for comparison purposes, women with mental disorders (n = 51) had a slightly but significantly shorter gestational age (39.2 ± 0.2 vs 39.8 ± 0.1 weeks, P = 0.003) and smaller birth weight (2993.0 ± 56.7 vs 3152.4 ± 23.6 g, P = 0.010) compared with the control group (n = 278). Intervention by psychiatrists was required for only 10 patients, and no patients required termination of pregnancy due to exacerbation of mental disorders. In schizophrenia patients who were taking atypical antipsychotics and benzodiazepine, a significant increase in maternal gestational weight gain, and a significant shorter gestational age were detected, respectively, compared with patients who were not receiving any drug treatments. CONCLUSION: A trend towards a lower birth weight and shorter gestational age was observed in Japanese women with well-controlled mental disorders, but the effect of well-controlled mental disorders on the perinatal outcome was minimal.