Effect of interleukin-6 on nucleated erythrocytes in lipopolysaccharide-induced preeclampsia rats / 解剖学报

Objective To explore the effect of interleukin (IL)-6 on nucleated erythrocytes in lipopolysaccharide (LPS)-induced preeclampsia rats. Methods ELISA and immunohistochemistry were used to detect the IL-6 in peripheral blood and placenta of preeclampsia and normal pregnancy; Flow cytometry and immunofluorescence were used to detect the maternal nucleated erythrocytes. Pregnant SD rats were randomly divided into 3 groups: the control, LPS and LPS +anti-IL-6 group; IL-6, the proportion of nucleated erythrocytes, JAK2/MEK and PI3K/Akt signal-related genes were detected. Results The IL-6 of preeclampsia was higher than that of normal patients. Compared with the Control group, IL-6, the proportion of nucleated erythrocytes and JAK2, P85, Akt, P65, IL-IB mRNA of LPS group increased, the fetal weight decreased; Compared with the LPS group, IL-6, the proportion of nucleated erythrocytes and JAK2, P85, Akt, P65 and IL-IB mRNA of the LPS + anti-IL-6 group decreased. Conclusion The up-regulation of IL-6 of preeclampsia patients is accompanied by increased nucleated erythrocytes in peripheral blood. Neutralizing IL-6 in vivo may down-regulate JAK2/ PI3K/Akt/NF-KB-signal-mediated IL-IB to protect preeclampsia rats.

Comparison of Umbilical Venous Erythropoietin Concentration Between Non-meconium Stained Neonates and Meconium Stained Neonates of Term Pregnancy / 대한주산의학회잡지

OBJECTIVE: To determine whether meconium staining can be the indicator of intrauterine hypoxia by comparing umbilical venous erythropoietin (EPO) concentration and the number of nucleated erythrocytes (NRBC), as a marker of intrauterine hypoxia, between non meconium-stained neonates and meconium-stained neonates of term pregnancy. And to determine correlation between the number of NRBC, EPO levels and interleukin-6 (IL-6), as another mediator of intrauterine hypoxia. METHODS: In 240 neonates with gestational age ranged from 37 to 41 weeks, including 231 cases of nonmeconium-stained neonates and 9 cases of meconium-stained neonates, we performed the measurement of EPO levels by RIA, the number of NRBC per 100 white blood cells (WBC) by blood smear and IL-6 by ELISA in umbilical venous blood at delivery. Statistical analysis was performed by chi-square test, Wilcoxon rank sum test, linear regression analysis using SPSS 11.0 version statistical package. RESULTS: Amniotic fluids of meconium-stained neonates had significantly greater EPO concentrations compared with that of nonmeconium-stained controls (41.3+/-13.0 vs 26.5+/-18.9 mIU/mL, p=0.001). But there were no statistical difference in the number of NRBC, IL-6 levels and hematocrit of umbilical venous blood. The EPO levels in umbilical venous blood was correlated with the number of nucleated erythrocytes (r2=7.7%, p<0.001), and IL-6 in umbilical venous blood was correlated with the number of NRBC. (r2=11.5%, p<0.001). CONCLUSION: These results suggest that meconium-stained amniotic fluid can be associated with fetal hypoxia. And the production of fetal NRBC is thought to be stimulated by EPO and IL-6, but it requires further study of other (yet to be determined) hypoxia-derived mediators.

Relationship between Oligohydrmanios and Umbilical Venous Blood Erythropoietin Levels and Nucleated Erythrocyte Counts in Appropriate and Small for Gestational Age Fetuses at Birth / 대한주산의학회잡지

OBJECTIVE: The purpose of this study is to assess the relationship between the oligohydramnios and umbilical venous blood EPO levels and nRBC counts, and to investigate the significance of oligohydramnios as intrauterine hypoxic marker in AGA and SGA fetuses. METHODS: EPO and nRBC were measured in 217 singletons with a gestational age of 32 to 42 weeks at delivery. The subjects were divided into 4 groups: group 1 (AGA with normal amniotic fluid volume, n=129), group 2 (AGA with oligohydramnios, n=15), group 3 (SGA with normal amniotic fluid volume, n=57) and group 4 (SGA with oligohydramnios, n=11). EPO levels and nRBC counts in group 2, 3 and 4 were compared to those in group 1 using Mann-Whitney U-test. Relationship between EPO and nRBC was assessed using linear regression analysis. In addition, relationship between results of umbilical venous blood gas analysis and EPO/nRBC was assessed using the same method. P-values less than 0.05 were considered statistically significant. RESULTS: EPO levels and nRBC counts in AGA with oligohydramnios (group 2) were not significantly different from those in AGA with normal amniotic fluid volume (group 1). EPO levels in SGA with normal amniotic fluid volume (group 3) were significantly higher than those in AGA with normal amniotic fluid volume (group 1). EPO levels and nRBC counts in SGA with oligohydramnios (group 4) were significantly higher than those in AGA with normal amniotic fluid volume (group 1). There was significant positive correlation between EPO and nRBC. Parameters obtained from the umbilical venous blood gas analysis were more related with nRBC than EPO. CONCLUSION: Oligohydramnios was significant intrauterine hypoxic marker in SGA fetuses. However, the results of this study suggested that the influence of oligohydramnios on antenatal fetal condition might be less severe in AGA fetuses than in SGA fetuses. Moreover, it was likely that nRBC had stronger association with pathologic hypoxia than EPO did.

Comparison of umbilical venous erythropoietin concentration between appropriate and small-for-gestational-age neonates of term pregnancy / 대한산부인과학회잡지

OBJECTIVE: To evaluate the intrauterine hypoxic effect in term small-for-date (SGA) neonates by comparing the umbilical venous erythropoietin (EPO) concentration between appropriately-grown (AGA) and SGA neonates at delivery and to determine the variables that correlate with the umbilical venous EPO concentration by multiple regression analysis. METHODS: 183 term singleton neonates (gestational weeks > OR =37) were enrolled and divided into 136 cases of AGA (10th-90th percentile of birth weight for the gestational age) and 47 cases of SGA (< 10th percentile of birth weight for the gestational age. At each delivery, blood gas values, concentration of EPO by radioimmunoassay and the number of nucleated erythrocytes (NRBC) per 100 white blood cells in smear of umbilical venous blood were obtained. The placentas were examined microscopically for presence of pathological infarct. Statistical analysis was done by Mann-Whitney U test, x2 test, and univariate and multiple regression analysis using SPSS statistical package (version 10). RESULTS: The median umbilical venous EPO concentration, fetal hemoglobin level were significantly higher in SGA neonates than those in AGA neonates. There was no difference in number of NRBC between AGA and SGA neonates. Multiple regression analysis model with level of NRBC, presence of placental infarct and SGA provided prediction of EPO level in umbilical venous blood at delivery (regression equation: EPO=-103.94+4.75NRBC+68.07placental infarct+36.40SGA F=15.57. r2=0.47). CONCLUSION: Term SGA neonates was considered to have compensatory, not pathological intrauterine hypoxic effect by showing increased level of EPO and normal level of NRBC in umbilical venous blood at delivery, compared with thoses of AGA. In the suspected cases of SGA antenatally, measurement of NRBC level and placental pathologic examination for infarct can be informative for estimating the extent and duration of intrauterine hypoxia.

Comparison of umbilical venous erythropoietin concentration between appropriate and small-for-gestational-age neonates of term pregnancy / 대한산부인과학회잡지

OBJECTIVE: To evaluate the intrauterine hypoxic effect in term small-for-date (SGA) neonates by comparing the umbilical venous erythropoietin (EPO) concentration between appropriately-grown (AGA) and SGA neonates at delivery and to determine the variables that correlate with the umbilical venous EPO concentration by multiple regression analysis. METHODS: 183 term singleton neonates (gestational weeks > OR =37) were enrolled and divided into 136 cases of AGA (10th-90th percentile of birth weight for the gestational age) and 47 cases of SGA (< 10th percentile of birth weight for the gestational age. At each delivery, blood gas values, concentration of EPO by radioimmunoassay and the number of nucleated erythrocytes (NRBC) per 100 white blood cells in smear of umbilical venous blood were obtained. The placentas were examined microscopically for presence of pathological infarct. Statistical analysis was done by Mann-Whitney U test, x2 test, and univariate and multiple regression analysis using SPSS statistical package (version 10). RESULTS: The median umbilical venous EPO concentration, fetal hemoglobin level were significantly higher in SGA neonates than those in AGA neonates. There was no difference in number of NRBC between AGA and SGA neonates. Multiple regression analysis model with level of NRBC, presence of placental infarct and SGA provided prediction of EPO level in umbilical venous blood at delivery (regression equation: EPO=-103.94+4.75NRBC+68.07placental infarct+36.40SGA F=15.57. r2=0.47). CONCLUSION: Term SGA neonates was considered to have compensatory, not pathological intrauterine hypoxic effect by showing increased level of EPO and normal level of NRBC in umbilical venous blood at delivery, compared with thoses of AGA. In the suspected cases of SGA antenatally, measurement of NRBC level and placental pathologic examination for infarct can be informative for estimating the extent and duration of intrauterine hypoxia.

Fetal cells in maternal blood for prenatal diagnosis.

Advances in molecular genetics have led to prenatal DNA diagnosis, using either invasive or noninvasive approach. Fetal cells are one of the sources for prenatal diagnosis. Standard prenatal genetic diagnosis currently involves chorion villus sampling (CVS) or amniocentesis, which are invasive techniques. Noninvasive methods such as maternal serum biochemical screening (triple markers) in combination with ultrasonography can now detect a large percentage of chromosomal and congenital anomalies. However their lack of optimal specificity and sensitivity compels the use of invasive techniques, which pose a small but significant risk of pregnancy loss. The presence of fetal cells in maternal circulation as early as 6 weeks of gestation has opened new avenues of noninvasive approach to prenatal diagnosis in identifying successfully both Chromosome and molecular genetic abnormalities. Several attempts have been made to detect and retrieve fetal nucleated cells including nucleated erythrocytes (NRBCs), leucocytes and trophoblasts in maternal blood. A number of clinical and laboratory studies are continuing throughout the world to determine the feasibility of isolation of fetal cells from maternal blood and its subsequent use in genetic diagnosis by FISH and PCR technology. This article thus reviews the latest literature on fetal cells from maternal blood with an intention of pursuing research with this novel noninvasive approach, which is the need of today in India.