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Background: We previously reported that fetal plasma erythropoietin (EPO) concentrations are significantly increased in growth-restricted fetuses with abnormal umbilical artery (UA) Doppler. During hypoxia in an ovine model, the primary site of fetal EPO synthesis was switched from the kidneys to the placenta. Therefore, we designed this study to evaluate human placental EPO gene expression and the correlation to fetal serum EPO concentration in growth-restricted fetuses in a monochorionic (MC) twin model., Methods: In MC twin pairs, selective intrauterine growth restriction (sIUGR) was defined as the presence of (i) birth weight discordance of > 20% and (ii) a smaller twin with a birth weight less than the 10th percentile. Fetal UA and middle cerebral artery (MCA) Doppler were checked within 1 week before delivery. An abnormal UA Doppler was defined as persistently absent or reverse end-diastolic flow. Cerebroplacental ratio (CPR) was defined as MCA-pulsatility index (PI)/UA-PI. Fetal plasma EPO concentrations were measured in cord blood, and EPO gene expression was assayed in each twin's placental territory. The intertwin plasma EPO ratio was calculated as the cord plasma EPO level of the smaller (or sIUGR) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin, and the intertwin placental EPO gene expression ratio was calculated similarly., Results: Twenty-six MC twins were analyzed, including normal twins (Group 1, n = 9), twins with sIUGR without UA Doppler abnormalities (Group 2, n = 9), and twins with sIUGR and UA Doppler abnormalities (Group 3, n = 8). The CPRs of smaller (sIUGR) fetuses were significantly decreased in Group 3 MC twins (p < 0.001), but not significantly different between Group 1 and Group 2. The highest fetal plasma EPO ratio and placental EPO gene expression ratio were identified in Group 3 MC twins (p < 0.001). The placental EPO gene expression ratios were significantly correlated with the fetal plasma EPO ratios (Pearson's correlation test, p = 0.004)., Conclusion: This study provides evidence of increased placental EPO expression in MC twin fetuses with sIUGR and abnormal UA Doppler. Future studies are needed to confirm the similar role of placental EPO in severe IUGR singletons.

Background: Placental mitochondrial DNA (mtDNA) has been proposed to be an indicator for placental hypoxia. This study was designed to evaluate the effect of vascular anastomoses between monochorionic (MC) twins on placental mtDNA., Methods: In this study, twin-twin transfusion syndrome (TTTS) treated with laser therapy and MC twins without TTTS (without laser therapy) resulting in two live babies were included in this study. The placental mtDNA fold changes (FC) between the small and large twins were analyzed using real-time quantitative PCR. TTTS twins with selective intrauterine growth restriction (sIUGR) are categorized as group 1, TTTS without sIUGR as group 2, MC twins without TTTS but with sIUGR as group 3, and MC twins without both TTTS and sIUGR as group 4., Results: There were seven cases in group 1, eight in group 2, 26 in group 3, and 24 in group 4 cases. The placental mtDNA FC were significantly higher in group 1 (1.57 ± 0.9) compared to that of the group 3 (0.86 ± 0.6)., Conclusion: In MC twin pregnancies with sIUGR, the placental mtDNA FC between the small and large twins are different between cases with and without inter-twin anastomoses. These findings suggest that the inter-twin anastomoses in the MC twins with sIUGR may provide rescue perfusion from the appropriate-for-gestational-age twin to the sIUGR one.

Objectives: To investigate placental autophagic activity in cases of twin-twin transfusion syndrome (TTTS) after successful laser therapy and to evaluate the effect of intertwin anastomoses on discordant placenta autophagic activity in monochorionic twins with one twin exhibiting selective intrauterine growth restriction., Materials and Methods: Placenta samples were prospectively obtained from 11 cases of successful TTTS post-laser therapy with two living babies. Among these infants, five infants had selective intrauterine growth restriction (sIUGR), based on the definition of a birth weight below the 10(th) percentile. After protein extraction, western blot tests were used to determine the amount of placenta microtubule-associated protein 1A/1B-light chain 3 (LC3)-II protein in the two individual placenta territories of the twin pair. The LC3-II protein fold change ratio (FCR) in a twin pair was defined as the LC3-II protein fold value over β-actin of the smaller twin divided by the LC3-II protein fold value over β-actin of the larger twin., Results: The LC3-II FCRs were not significantly different between TTTS with sIUGR and TTTS without sIUGR, after successful laser therapy., Conclusion: The discordance of placenta autophagic activity in the monochorionic twin with sIUGR was reduced after laser coagulation of the intertwin anastomoses, which may result from the effect of correction of the discordant intertwin placenta perfusion., (Copyright © 2015. Published by Elsevier B.V.)

Subject: This study investigates the placental autophagic activity in growth-restricted fetuses in the monochorionic (MC) twin model., Patients and Methods: Forty MC twins were prospectively enrolled in this study, including 21 with and 19 without selective intrauterine growth restriction (sIUGR), defined as birth weight below the tenth percentile. The sIUGR group was subdivided on the basis of present versus absent or reversed umbilical artery end-diastolic flow at Doppler. Placenta samples were taken after delivery from each twin placenta territories. After protein extraction, Western blot was used to determine light chain 3 (LC3)-II placental protein expression in sIUGR and appropriately grown (appropriate-for-gestational age, AGA) twins., Results: The LC3-II was significantly higher in the sIUGR twin placental territory than in their AGA counterparts. In the sIUGR group, LC3-II fold change was significantly increased compared with that in the AGA cotwins (2.28 vs 1.04, p < 0.05). Placental LC3-II protein expression was particularly stimulated in the MC sIUGR group with abnormal umbilical artery Doppler flow compared with AGA controls (p < 0.05, one-way analysis of variance test)., Conclusions: In MC twins, the placental autophagic activity is different between sIUGR and AGA cotwins. The placenta territory with the least blood flow perfusion has the highest autophagic activity., (© 2013 John Wiley & Sons, Ltd.)

This study was designed to evaluate the degree of placenta share discordance in relation to the betamethasone-induced return of positive end-diastolic flow in monochorionic twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler. Monochorionic twins with sIUGR was defined as one twin having an estimated fetal weight below the 10th percentile combined with an estimated fetal weight discordance >25%. The umbilical artery Doppler directly prior to (D0) and 24 hours (D1) and 48 hours (D2) after the first dose of betamethasone administration was recorded. The estimated individual placental weight in monochorionic twins was obtained by cutting the placenta along the vascular equator into two territories; the placenta share discordance was calculated as [(estimated individual placental weight of appropriated for gestational age twin- estimated individual placental weight of growth restricted twin)/estimated individual placental weight of appropriated for gestational age twin] × 100%. Six (23.1%) of the 26 included cases achieved betamethasone-induced return of positive umbilical artery end-diastolic flow. The difference of placenta share discordance and birth weight discordance were not significantly different between twins with and without betamethasone-induced return of positive umbilical artery end-diastolic flow. Thus, according to our study results, it was proposed that although the placenta share discordance correlated with the abnormal umbilical artery Doppler in the IUGR fetus in monochorionic twin, the betamethasone-induced return of positive umbilical artery end-diastolic flow, however, did not reveal the similar relationship with the severity of placenta share discordance.

Labor and its associated pain are thought to have unique impacts on parturient women. The goal of this study was to investigate the effects of labor and associated pain on differential gene expression profiles in the maternal, fetal, and placental compartments. We used microarrays to analyze maternal blood (MB), fetal cord blood (CB), and placental tissue samples in pregnant women after term vaginal deliveries (laboring group) and in term pregnant women after scheduled Ceasarean sections (nonlaboring group). The upregulated genes in the MB of the laboring group are involved in cytokine and nuclear factor-kappa B signaling pathways, regulation of the networks of toll-like receptor 4, and suppressor of cytokine signaling 3. Upregulated genes in the CB of the laboring group are involved in responding to stress and stimuli by regulating the network genes of the T-cell receptor beta locus and the FK506 binding protein 8. Differentially expressed genes in the placenta of the laboring group are involved in nitric oxide transport, gas transport, response to hydrostatic pressure, oxygen transport, acute phase responses, and the tumor necrosis factor-mediated signaling pathway, which are important during the transient hypoxemia and hypoperfusion that occur in the placenta during uterine contractions. Interestingly, few of the genes exhibited simultaneous changes in all three compartments, indicating that different pathways and complex interactions may be involved in human labor. In conclusion, human labor and its associated pain elicit unique gene regulatory changes in MB, placenta, and CB., (Copyright © 2011. Published by Elsevier B.V.)

Objective: To explore the changes in placental gene expression between women with preeclampsia and those with superimposed preeclampsia on chronic hypertension., Materials and Methods: In Taiwanese population, we compared gene expression between the placentas from preeclamptic patients and those with superimposed preeclampsia on chronic hypertension., Results: Although top-ranked activated genes between preeclampsia and superimposed preeclampsia on chronic hypertension were different, functional network analyses indicate that these genes are mainly involved in the regulation of cell death and apoptosis. These results suggest that apoptosis and other types of cell death in the placenta are common consequences of both diseases. However, placental endoglin (ENG) was expressed at a significantly higher level in preeclampsia than in superimposed preeclampsia. Results of functional network analysis indicated that ENG may play a role in the pathogenesis of preeclampsia through its interference with the endothelial nitric oxide synthase-regulated vasodilation., Conclusion: Our results support the fact that ENG is the culprit for the development of preeclampsia. In addition, this study identifies several other genes in the placenta, which are transcriptionally regulated in pregnancy-related hypertensions., (Copyright © 2011. Published by Elsevier B.V.)

This study was conducted to investigate the relationship among umbilical venous volume flow, birthweight and placental share in monochorionic twins with or without selective growth restriction. Having excluded cases complicated with twin-to-twin transfusion syndrome and one co-twin suffering intrauterine fetal death, a total of 51 monochorionic twin pregnancies were divided into two groups as with (group 1) and without (group 2) selective intrauterine growth restriction. Umbilical venous volume flow was calculated by multiplying the umbilical vein cross-sectional area by half of the maximal velocity around mid-trimester. The placentas were cut along the vascular equator into two individual placental masses. The discordance of birthweight was calculated as [(birthweight of larger twin-birthweight of smaller twin)/birthweight of larger twin 100%]. The discordances of umbilical venous volume flow and placental share were calculated in a similar fashion. The median umbilical venous volume flow discordances (68.4% and 15.3% in groups 1 and 2 monochorionic twins, respectively) were similar and correlated well with the placental share discordances (66.6% and 18.5% in groups 1 and 2 monochorionic twins, respectively) but not with the birthweight discordance (28.6% and 6.4% in groups 1 and 2 monochorionic twins, respectively) in both groups. We concluded that the umbilical venous volume flow discordance reflects the placental share discordance rather than the birthweight discordance in monochorionic twin pregnancies.

Objective: To evaluate the clinical outcome and placental territory ratio in monochorionic diamniotic (MCDA) twin pregnancies and selective intrauterine growth restrictions (sIUGR) with different types of umbilical artery (UA) Doppler., Study Design: An MCDA twin pregnancy with sIUGR was defined as a fetal weight below the 10th percentile in one twin. MCDA twins were divided into three groups: without IUGR (group I); with sIUGR, and a normal UA Doppler (group II); or an abnormal UA Doppler (persistent absence or reverse of end-diastolic velocity) (group III). Placental territory was calculated as the estimated individual placental mass/total placenta weight., Results: Altogether, 27 cases of group I, 11 cases of group II and 13 cases of group III MCDA twins were included. The placenta territory of the IUGR twin in group III MCDA twin was the smallest among the three groups of MCDA twins (ANOVA test, p < 0.001). There was incidence of neonatal death in six (6/26) of group III MCDA fetuses, while none in groups I and II MCDA twins did., Conclusions: In MCDA twins with sIUGR, abnormal UA Doppler in the IUGR twin may reflect a more severe unequal placenta share and poorer neonatal outcomes. The prognosis of group II MCDA twins, even with sIUGR found in early gestation, is, by contrast, better.

Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia. [ABSTRACT FROM AUTHOR]

Abstract: We compared microRNA profiles between choriocarcinoma and non-cancerous trophoblasts, and revealed that miR-199b was underexpressed in choriocarcinoma. By computational prediction and microarray studies, SET (protein phosphatase 2A inhibitor) was shown to be one of the target genes regulated by miR-199b. Ectopic expression of miR-199b inhibited endogenous SET protein levels and the activity of the luciferase reporter containing the 3′-UTR of SET. Further comparisons of formalin-fixed paraffin-embedded human choriocarcinoma, mole, and non-cancer trophoblast tissues confirmed the initial findings of low miR-199b expression and SET upregulation in choriocarcinomas, suggesting that microRNA-dysregulated SET protein may account for the rapid growth seen with choriocarcinomas. [Copyright &y& Elsevier]