Bell Research Center for Reproductive Health and Center

Nagoya-shi, Japan

Bell Research Center for Reproductive Health and Center

Nagoya-shi, Japan
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Tsuda H.,Nagoya University | Kotani T.,Nagoya University | Sumigama S.,Nagoya University | Mano Y.,Nagoya University | And 6 more authors.
Early Human Development | Year: 2014

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 36-38. weeks 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 36-38. weeks of gestation. © 2013 Elsevier Ireland Ltd.


Kotani T.,Nagoya University | Iwase A.,Nagoya University | Tsuda H.,Nagoya University | Mano Y.,Nagoya University | And 9 more authors.
Biology of Reproduction | Year: 2013

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. © 2013 by the Society for the Study of Reproduction, Inc.


Erkhembaatar L.O.,Nagoya University | Kotani T.,Nagoya University | Sumigama S.,Nagoya University | Tsuda H.,Nagoya University | And 10 more authors.
Placenta | Year: 2013

Introduction: Sphingosine-1-phosphate (S1P), a bioactive lipid, has been reported to regulate inflammation processes. The onset of labor is thought to be related to inflammation. We therefore hypothesized that S1P might be involved in the onset of labor. Methods: The expression of sphingosine kinase (SPHK)-1, which produces S1P, and S1P lyase (SPL)-1, which irreversibly inactivates S1P, were examined in the fetal membranes. The expression levels were compared between amnions from cases of elective Caesarean deliveries (pre-labor) and those from vaginal deliveries (post-labor). In primary cultured human amnion cells, the expression levels of prostaglandin-endoperoxide synthase (PTGS)-2 were examined in the presence or absence of S1P treatment. Results: SPHK-1 and SPL-1 were both expressed in the amnion. The expression of SPHK-1 in the post-labor amnions increased compared with that in the pre-labor amnions. The expression of PTGS-2, a key regulator of labor, also increased in the post-labor amnion. However, the SPL-1 expression in the pre-labor amnion was not significantly different from that in the post-labor amnion. S1P1-3 and 5, which were coupled with Gi protein, were consistently found in the amnion cells. The treatment with S1P increased the expression of PTGS-2, and this was completely suppressed by a Gi inhibitor in the amnion cells. Discussion: We are herein provide the first evidence of increased SPHK-1 expression in post-labor amnions, and that S1P increases the PTGS-2 expression in amnion cells. Conclusions: Our results suggest that S1P might play a role in the onset of labor via the induction of PTGS-2. © 2013 Elsevier Ltd. All rights reserved.


Tsuda H.,Nagoya University | Kotani T.,Nagoya University | Sumigama S.,Nagoya University | Mano Y.,Nagoya University | And 4 more authors.
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2016

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. © 2015 Taylor & Francis.


Tsuda H.,Nagoya University | Kotani T.,Nagoya University | Sumigama S.,Nagoya University | Mano Y.,Nagoya University | And 3 more authors.
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2015

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. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.


Hirako S.,Nagoya University | Tsuda H.,Nagoya University | Kotani T.,Nagoya University | Sumigama S.,Nagoya University | And 6 more authors.
Phytotherapy Research | Year: 2016

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. Copyright © 2016 John Wiley & Sons, Ltd.


Tsuda H.,Nagoya University | Kotani T.,Nagoya University | Nakano T.,Nagoya University | Imai K.,Nagoya University | And 3 more authors.
Clinica Chimica Acta | Year: 2016

Background Congenital diaphragmatic hernia (CDH) causes pulmonary hypoplasia, which are often fatal. We established a new biomarker for fetal lung hypoplasia in CDH. Methods We collected newborn lung tissue specimens at E21 from normal and nitrofen-induced CDH rats (administered 100 mg orally at E9) and performed a microarray analysis and real-time PCR (RT-PCR). Sixty-three human amniotic fluid (AF) samples, including samples from isolated CDH cases (n = 33) and Cesarean section (CS) cases without fetal complications (controls) (n = 30), were obtained. All AF samples were obtained at the time of CS, which was performed after 35–38 gestational weeks, from April 2007 to January 2016. Results A microarray analysis and RT-PCR showed decreased gene expression levels of lipocalin 2 (LCN2) in the nitrofen-induced CDH lungs (p < 0.05). We next examined the LCN2 levels in human AF samples using ELISA and the levels were significantly lower in the CDH cases than in controls (73.7 ng/ml vs 163.8 ng/ml; p < 0.05). A significant positive correlation was observed between the amniotic LCN2 level and the observed/expected lung-to-head ratio (p < 0.001). Conclusions LCN2 may be a potentially useful biomarker for lung hypoplasia in a rat and human CDH. © 2016 Elsevier B.V.


PubMed | Bell Research Center for Reproductive Health and Center and Nagoya University
Type: | Journal: Clinica chimica acta; international journal of clinical chemistry | Year: 2016

Congenital diaphragmatic hernia (CDH) causes pulmonary hypoplasia, which are often fatal. We established a new biomarker for fetal lung hypoplasia in CDH.We collected newborn lung tissue specimens at E21 from normal and nitrofen-induced CDH rats (administered 100mg orally at E9) and performed a microarray analysis and real-time PCR (RT-PCR). Sixty-three human amniotic fluid (AF) samples, including samples from isolated CDH cases (n=33) and Cesarean section (CS) cases without fetal complications (controls) (n=30), were obtained. All AF samples were obtained at the time of CS, which was performed after 35-38 gestational weeks, from April 2007 to January 2016.A microarray analysis and RT-PCR showed decreased gene expression levels of lipocalin 2 (LCN2) in the nitrofen-induced CDH lungs (p<0.05). We next examined the LCN2 levels in human AF samples using ELISA and the levels were significantly lower in the CDH cases than in controls (73.7ng/ml vs 163.8ng/ml; p<0.05). A significant positive correlation was observed between the amniotic LCN2 level and the observed/expected lung-to-head ratio (p<0.001).LCN2 may be a potentially useful biomarker for lung hypoplasia in a rat and human CDH.

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