Association between fetal growth restriction and maternal exposure to polybrominated diphenyl ethers.

Humans are exposed to polybrominated diphenyl ethers (PBDEs) via ingestion of food, dust inhalation, and dermal absorption. Exposure to PBDEs via the placenta and breast milk is a special and important pathway in infants. This nested case-control study aimed to investigate the levels of PBDEs in maternal serum and colostrum, and to assess the association between the occurrence of fetal growth restriction (FGR) and prenatal exposure to PBDEs. We recruited 293 mother-newborn pairs, including 98 FGR cases and 195 healthy controls in Wenzhou, China. Maternal serum and colostrum samples were collected during pregnancy and after delivery, respectively, and the levels of PBDEs were measured by gas chromatography-tandem mass spectrometry. The total levels of PBDEs in maternal serum and colostrum were found to be in equilibrium, but congener profiles of PBDEs in these matrices were different. Increased BDE-207, BDE-209, ∑BDE196-209 and ∑PBDEs levels in maternal serum and BDE-99, ∑BDE17-154 and ∑PBDEs levels in colostrum were correlated with decreased birth weight Z score. Increased concentrations of higher brominated BDEs in maternal serum (odds ratio (OR) = 1.010, 95%CI = 1.003-1.018) and low-to moderately brominated BDEs in colostrum (OR = 1.004, 95%CI = 1.000-1.009) were associated with increased risk of FGR, which showed an exposure-response relationship. In addition, infants with FGR were more exposed to PBDEs in colostrum after birth than healthy infants. Longitudinal birth cohort studies are needed to determine the prolonged effect of PBDEs exposure on the growth of FGR infants in the future.

Related factors and adverse neonatal outcomes in women with preterm premature rupture of membranes complicated by histologic chorioamnionitis.

BACKGROUND: The aim of this study was to identify factors predicting histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM). MATERIAL AND METHODS: We retrospectively enrolled 371 women diagnosed with PPROM at less than 34 weeks of gestation at the Second Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2012. HCA was diagnosed by placental histopathology in 70% of participants. Binary logistic regression was used to identify factors associated with HCA and neonatal outcomes. RESULTS: Patient age, rate of parity, tocolysis, cesarean section, serum C reactive protein (CRP) level at admission, white blood cell count, and latency duration did not significantly differ between the 2 groups. Binary logistic regression revealed that oligohydramnios at admission, gestational age at PPROM, and serum CRP >8 mg/L before delivery were significantly associated with HCA. Gestational age at delivery and birth weight were significantly lower in HCA patients than control patients. The rate of 1-min Apgar score <7, abnormal neonatal intracranial ultrasound findings, neonatal pneumonia, bronchopulmonary dysplasia, early-onset neonatal sepsis, and mortality were higher in HCA patients, but no significant difference was observed in the incidence of neonatal respiratory distress syndrome, necrotizing enterocolitis, hyperbilirubinemia, or hypoglycemia. CONCLUSIONS: Younger gestational age at time of PPROM, higher CRP level before delivery, and oligohydramnios at admission in women with PPROM are associated with HCA, and HCA is associated with some adverse neonatal outcomes.

[Regulation of aquaporin 3 protein expression in amnion epithelial cells through cAMP-PKA signal pathway].

OBJECTIVE: To investigate the expression of aquaporins-3 (AQP3) in amniotic epithelial cells regulated by cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signal pathway and to explore the mechanisms of its expression. METHODS: The amniotic epithelial cells were collected from 30 patients who underwent elective caesarean sections at term with normal amniotic fluid volume and primarily cultured. The cultured cells were treated with (1)forskolin groups: different concentration (0, 2.5, 5, 50 or 100 µmol/L) of forskolin treated cells for 2 hours, and the optimal concentration of forskolin treated cells with different time (0, 1, 2, 10 or 20 hours); (2)SP-cAMP groups: different concentration (0, 2.5, 5, 50 or 100 µmol/L) of SP-cAMP treated cells for 2 hours, and the optimal concentration of SP-cAMP treated cells with different time (0, 1, 2, 10 or 20 hours); (3)H-89 groups: different concentration (0, 5, 10, 50 or 100 µmol/L) of H-89 treated cells for 2 hours, and the optimal concentration of H-89 treated cells with different time (0, 1, 2, 10 or 20 hours ). The level of intracellular cAMP and activity of PKA were detected by using ELISA, and immunohistochemistry was used to detect the localization of AQP3, the protein expression of total cAMP-response element binding protein (CREB) and phospho-CREB (p-CREB) and AQP3 were assessed by western blot analysis. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay. RESULTS: (1) The brown staining of AQP3 was detected in both cell membrane and cytoplasm in each group. (2) There was no significant change of the cell proliferation rate among groups with different concentration of forskolin, SP-cAMP and H-89 treatment (P > 0.05). (3) After different concentration of forskolin treated 2 hours, the expression of total CREB had no significant difference among them(P > 0.05). While the expression of cAMP level, PKA activity, p-CREB and AQP3 protein were significantly changed, which were higher in 2.5 µmol/L, 5 µmol/L, 50 µmol/L forskolin group when compared with 0 µmol/L (P < 0.05). Their expressions in 5 µmol/L forskolin group were higher than that in 2.5 µmol/L and 50 µmol/L (P < 0.05). The optimal forskolin concentration was 5 µmol/L. (4) After different concentration of SP-cAMP treated 2 hours, the expression of total CREB and cAMP level had no significant difference among them (P > 0.05), while the expression of PKA activity, p-CREB and AQP3 protein were significantly changed, which were higher in 5 µmol/L, 50 µmol/L SP-cAMP group when compared with 0 µmol/L (P < 0.05). Their expressions in 50 µmol/L SP-cAMP group were higher than that in 5 µmol/L (P < 0.05). The optimal SP-cAMP concentration was 50 µmol/L. (5) After different concentration of H-89 treated 2 hours, the expression of total CREB and cAMP level had no significant difference among them (P > 0.05), while the expression of PKA activity, p-CREB and AQP3 protein were significantly changed, which were lower in 10 µmol/L, 50 µmol/L and 100 µmol/L H-89 group when compared with 0 µmol/L (P < 0.05). Their expressions in 10 µmol/L H-89 group were lower than that in 50 µmol/L, 100 µmol/L (P < 0.05). The optimal H-89 concentration was 10 µmol/L. (6) p-CREB and AQP3 protein expression were significantly lower in 5 µmol/L forskolin combined 10 µmol/L H-89 incubating 2 hours group when compared with 5 µmol/L forskolin, but higher than that in 10 µmol/L H-89 treated group (P < 0.05). Total CREB was no significant difference among the three groups (P > 0.05). CONCLUSION: cAMP-PKA signal transduction pathway may regulate AQP3 protein expression in human amniotic epithelial cells.

[11beta-hydroxysteroid dehydrogenase type 2 enzyme activity effect after exposures phthalate esters in maternal].

OBJECTIVE: To study the association between phthalate esters (PAEs) metabolites in maternal urine and 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2 ) enzyme activity, explore the possible mechanism of PAEs effect on fetal development. METHODS: All of 33 cases of intrauterine growth retardation (IUGR) newborn were selected by random sampling in 2012. And 33 cases of normal control newborn were enrolled, use high performance liquid chromatography-tandem mass spectrometry method was used to detect 4 kinds of phthalate esters (PAEs) metabolites in maternal urine: mono-n-butyl phthalate ester (MBP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and three kinds of cortisol corticosterone metabolites, tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone (THE), and analyze the association between phthalate esters (PAEs) metabolites in maternal urine and 11ß-HSD2 enzyme activity. RESULTS: MBP, MEHP, MEHHP, MEOHP metabolites can be detected in 98% (65 cases) , 89% (59 cases), 91% (60 cases), 91% (60 cases) of all 66 maternal urine samples, respectively. The median concentrations of test material in case group were 31.20 ng/ml for MBP, 24.61 ng/ml for MEHHP, 11.72 ng/ml for MEOHP and 48.67 ng/ml for SumDEHP which were significantly higher than those of the control group (were 17.32, 12.03, 5.68 and 28.64 ng/ml); 11ß-HSD2 activity in case group ((THF+allo-THF)/THE = (0.79 ± 0.09) ng/ml) was significantly lower than that of the control group((THF+allo-THF)/THE = (0.58 ± 0.04) ng/ml); PAEs metabolites MBP (ß' = 1.12), MEHHP(ß' = 1.14), MEOHP(ß' = 1.10), SumDEHP(ß' = 1.08) in baby boy mother's urine was reversely correlated to 11ß-HSD2 activity. CONCLUSIONS: PAEs could affect fetal development by inhibit 11ß-HSD2 activity.

[Compound danshen injection regulated the expression of AQP3 in the human amnion epithelium cells through JNK signal pathway].

OBJECTIVE: To explore the role of Compound Danshen Injection (CDI) in regulating the expression of aquaporin 3 (AQP3) in human amnion epithelium cells (hAECs), and to study the relation between c-Jun N-terminal kinase (JNK) signal pathway and AQP3. METHODS: hAECs were isolated and primarily cultured from term pregnancy with normal amniotic fluid volume and from term pregnancy with oligohydramnios, and then hAECs were further divided into four groups, i.e., the blank control group (A), the SP600125 group (B), the CDI group (C), and the SP600125 +CDI group (D). The cell viability was measured by cell counting kit-8 assay (CCK-8). The expression of total JNK, phosphorylated JNK, and AQP3 were determined by Western blot. RESULTS: (1) In hAECs with normal AFV or with oligohydramnios: There was no statistical difference in the cell viability or the expression of total JNK among the 4 groups (P > 0.05). But there was statistical difference in the expression of p-JNK (P < 0.05). Compared with A group, the expression of p-JNK was obviously down-regulated in B group, but obviously up-regulated in C group (P < 0.05). The expression of p-JNK was significantly lower in D group than in C group, but higher than that in A group or B group (P < 0.05).The AQP3 expression in the hAECs with normal amniotic fluid volume of C group and D group were higher than that in the A group (P < 0.05). However, there was no statistical difference in the AQP3 expression between C group and D group (P > 0.05). In hAECs with oligohydramnios, the expression of AQP3 obviously decreased in B group, but up-regulated in C group (both P < 0.05). The expression of AQP3 was lower in D group than in C group, but higher than in B group (P < 0.05). CONCLUSION: CDI could regulate the AQP3 expression in hAECs with oligohydramnios via activating the JNK signal pathway.

MCU promotes the migration of glioma cells by activating p38 through TFEB-mediated autophagy.

Changes in calcium signalling are crucial for the development of glioma cells. Whether mitochondrial calcium balance is involved in glial cell development is still unknown. Mitochondrial Calcium Uniporter (MCU) plays an important role in regulating glioma progression. In this work, we found that MCU and p38 expression were positively correlated with glioma grade and the degree tumour progression. MCU increases glioma cell migration by upregulating p38. Furthermore, p38 promotes glioma progression by activating Transcription Factor EB (TFEB)-mediated autophagy. Thus, MCU promotes glioma cell migration by activating autophagy in a p38/TFEB pathway-dependent manner, which provides a theoretical basis for new therapeutic targets for gliomas.

[Investigation of iron deficiency status in the newborns of gestational diabetes mellitus women].

OBJECTIVE: To investigate the iron status in the newborns of maternal gestational diabetes mellitus (GDM) women, and explore the mechanism of iron deficiency in these newborns. METHODS: From June 2008 to October 2011, 64 GDM women (GDM group) and 71 healthy pregnant women (control group) who delivered in the Second Affiliated Hospital of Wenzhou Medical College and their newborns were studied prospectively. Serum ferritin (SF), serum transferrin receptor (sTfR), erythropoietin (Epo), haemoglobin (Hb), serum level of insulin and plasma glucose in cord blood was measured. The neonatal birth weight (BW) and birth weight Z Score (WAZ) was recorded. The concentrations of serum fasting insulin (FINS), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) were tested for all the women before delivery. RESULTS: In the GDM group, the cord blood sTfR, Epo and serum level of insulin was (42 ± 10) nmol/L, (56 ± 41) U/L and (18 ± 5) U/L, respectively. While in the control group, these were (35 ± 8) nmol/L, (41 ± 43) U/L and (10 ± 5) U/L, respectively. The cord blood sTfR, Epo and serum level of insulin in the GDM group were significantly higher than those in the control group (P < 0.05). The cord blood SF in the GDM group [(60 ± 36) µg/L] was significantly lower than that of the control group [(146 ± 38) µg/L, P < 0.01]. The neonatal BW and WAZ in the GDM group [(3615 ± 538) g and 0.558] were significantly higher than those in the control group [(3449 ± 423) g and 0.224, P < 0.05]. No significant difference was found in the cord blood plasma glucose and Hb between the GDM group [(3.3 ± 1.0) mmol/L and (181 ± 18) g/L] and the control group [(3.0 ± 0.8) mmol/L and (176 ± 16) g/L, P > 0.05]. The FINS and HbA1c of the GDM group [(12.5 ± 5.0) U/L and (6.5 ± 0.7)%] were significantly higher than those in the control group [(10.9 ± 4.3) U/L and (5.3 ± 0.7)%, P < 0.05]. The FPG of the GDM group and the control group were (5.3 ± 1.2) and (5.0 ± 1.0) mmol/L, respectively, with no statistically significant difference (P > 0.05). CONCLUSION: Maternal GDM may related to the iron deficiency of the newborns.

[The role of MAPK signal pathway in the regulation of AQP3 expression induced by compound danshen injection in human amniotic epithelial cells].

OBJECTIVE: To investigate the role of mitogen-activated protein kinases (MAPKs)-extracellular signal regulated kinase1/2 (ERK1/2) signal pathway in the regulation of Compound Danshen Injection (CDI) induced AQP3 expression in the human amniotic epithelial cells (hAECs). METHODS: hAECs of term pregnancy with normal amniotic fluid volume (AFV) or isolated oligohydramnios were primarily cultured. And the cells were equally divided into four groups, i.e., the vehicle control group, the U0126 group, the CDI group, the CDI + U0126 group. The expressions of phosphorylated ERK1/2 (p-ERK1/2) and AQP3 in hAECs were detected using Western blot analysis. RESULTS: (1) When compared with the control group, the expression level of p-ERK1/2 in hAECs in those with normal AFV and oligohydramnios obviously decreased in the U0126 group (P < 0.05). The expression level of p-ERK1/2 could be elevated in the CDI group (P < 0.05). The expression level of p-ERK1/2 in hAECs was higher in the CDI +U0126 group than in the U0126 group, but lower in the CDI + U0126 group than in the CDI group (P < 0.05). (2) There was no obvious change in AQP3 expression in hAECs with normal AFV between the U0126 group and the vehicle control group (P > 0.05). There was no statistical difference in the expression level of AQP3 between the CDI group and the U0126 +CDI group (P > 0.05), but they were higher than those in the vehicle control group (P < 0.05). (3) Compared with the vehicle control group, the expression level of AQP3 in hAECs with oligohydramnios significantly decreased in the U0126 group and increased in the CDI group (P < 0.05). The expression level of AQP3 was lower in the U0126 + CDI group than in the CDI group, but higher in the U0126 +CDI group than in the U0126 group (P < 0.05). CONCLUSION: CDI could regulate AQP3 expression level in hAECs with oligohydramnios via activating the MAPK-ERK1/2 signal transduction pathway.

[Effects of compound salvia miltiorrhiza injection on aquaporin 3 expression in human amniotic epithelial cells].

OBJECTIVE: To study the effects of Compound Salvia miltiorrhiza Injection (CSI) on aquaporin 3 (AQP3) expression in human amniotic epithelial cells (hAECs), and to explore its mechanisms for treating oligohydramnios. METHODS: The hAECs selected from 8 human term pregnancies with oligohydramnios and no other complications (as the test group)and 8 human term pregnancies with normal amniotic fluid volume (as the control group) were primarily cultured. The mRNA and protein expressions of AQP3 in hAECs were detected using reverse transcription-polymerase chain reaction and Western blot with various concentrations of CSI (0.000, 0.001, 0.010, 0.020, 0.060, and 0.100 mg/mL, respectively) at different time points (0, 6, 12,24, and 48 h, respectively). RESULTS: (1) Compared with the control group, the AQP3 expression was down-regulated in the test group (P < 0.05). (2) The AQP3 expression in the two groups reached the peak when the concentration of CSI was 0.010 mg/mL, showing statistical difference when compared with other concentrations (P < 0.05). (3) The AQP3 expression reached the peak when 0.010 mg/mL CSI acted for 12 h, showing statistical difference when compared with other concentrations (P < 0.05). (4) The AQP3 expression was up-regulated in the two groups when 0.010 mg/mL CSI acted for 12 h. But the up-regulated AQP3 expression was more obvious in the test group than in the control group (P < 0.05). CONCLUSIONS: CSI could regulate the AQP3 expression in hAECs. CSI showed more obvious effects on the AQP3 expression in hAECs of oligohydramnios human term pregnancies.

[Factors and neonatal outcomes associated with histologic chorioamnionitis after premature rupture of membranes in the preterms].

OBJECTIVE: To investigate factors and neonatal outcomes associated with histologic chorioamnionitis (HCA) in preterm premature rupture of membranes (PPROM). METHODS: From Jan. 2008 to Jun. 2011, 230 women with PPROM at 28 - 33(+6) weeks of gestation undergoing deliveries in the Second Affiliated Hospital of Wenzhou Medical College were studied retrospectively. According to placental histopathologic findings, those patients were categorized into two groups, including 138 cases in histologic chorioamnionitis (HCA group) and 65 cases in non-chorioamnionitis (control) group. Age, parity, gestational age of PPROM and delivery, latency period, oligohydramnios, white blood cell (WBC) count and serum C-reactive protein (CRP) level at admission and before delivery, the incidence of neonatal respiratory distress syndrome (NRDS), neonatal pneumonia, bronchopulmonary dysplasia, necrotizing enterocolitis, early-onset neonatal sepsis, abnormal brain sonography findings and mortality were compared between two groups. RESULTS: (1) The incidence of HCA was 68.0% (138/203) in all 203 cases with PPROM. (2) The occurring ruptured membrane gestation in HCA group was (31.1 ± 1.5) weeks, which were significantly earlier than (32.0 ± 1.3) weeks in control group (P < 0.05). The level of CRP of (8.2 ± 14.9) mg/L before delivery in HCA group was significantly higher than (5.5 ± 7.2) mg/L in control group (P < 0.05). The rate of oligohydramnios and cesearean sections were 55.1% (76/138) and 45.7% (63/138) in HCA group, which were significantly higher than 30.8% (20/65) and 29.2% (19/65) in control group (P < 0.05). There were no significant difference in patient's age, parity, WBC count and CRP at admission between two groups (P > 0.05). The latency period did not show significant difference between (140 ± 116) hours in HCA group and (129 ± 125) hours in control group (P > 0.05). (3) Using multivariable logistic regression models, oligohydramnios (OR = 2.937), gestational age of PPROM < 32 weeks (OR = 2.352), serum CRP level > 8 mg/L before delivery (OR = 4.923) and latency period > 48 - 168 hours (OR = 4.439) were significantly associated with HCA (P < 0.05). (4) The gestational age of delivery and birth weight of HCA group were significantly lower than those of control group [(32.0 ± 1.5) weeks vs. (32.7 ± 1.5) weeks, (1680 ± 379) g vs. (2017 ± 333) g, respectively, P < 0.05]. The incidence of Apgar < 7, abnormal brain sonograhy findings, neonatal pneumonia, bronchopulmonary dysplasia, early-onset neonatal sepsis and mortality in HCA group were significantly higher than those in control group [20.3% (28/138) vs. 7.7% (5/65), 14.5% (20/138) vs. 4.6% (3/65), 12.3% (17/138) vs. 3.1% (2/65), 5.8% (8/138) vs. 0, 6.5% (9/138) vs. 0, 12.3% (17/138) vs. 3.1% (2/65), respectively, P < 0.05]. The incidence of necrotizing enterocolitis (1.5%, 2/138) in HCA group was higher than that of control group (0) and the incidence of NRDS (18.8%, 26/138) in HCA group did not show statistical difference with 21.4% (14/65) in control group (P > 0.05). CONCLUSIONS: It was found that HCA was significantly correlated with lower gestational age of PPROM, higher serum CRP level before delivery, prolonged latency period and oligohydramnios in PPROM. HCA could increase the neonatal morbidity and mortality.