Circulation In Pregnancy Research Articles

Preconception maternal retinal venular widening and steeper resistance increments in the utero-fetoplacental circulation in pregnancy

Preconception maternal retinal venular widening and steeper resistance increments in the utero-fetoplacental circulation in pregnancy

The effect of prone positioning on maternal haemodynamics and fetal wellbeing in the third trimester-A primary cohort study with a scoping review.

Supine sleep position is associated with stillbirth, likely secondary to inferior vena cava compression, and a reduction in cardiac output (CO) and uteroplacental perfusion. Evidence for the effects of prone position in pregnancy is less clear. This study aimed to determine the effect maternal prone position on maternal haemodynamics and fetal heart rate, compared with left lateral position. Twenty-one women >28 weeks' gestation underwent non-invasive CO monitoring (Cheetah) every 5 minutes and continuous fetal heart rate monitoring (MONICA) in left lateral (20 minutes), prone (30 minutes), followed by left lateral (20 minutes). Anxiety and comfort were assessed by questionnaires. Regression analyses (adjusted for time) compared variables between positions. The information derived from the primary study was used in an existing mathematical model of maternal circulation in pregnancy, to determine whether occlusion of the inferior vena cava could account for the observed effects. In addition, a scoping review was performed to identify reported clinical, haemodynamic and fetal effects of maternal prone position; studies were included if they reported clinical outcomes or effects or maternal prone position in pregnancy. Study records were grouped by publication type for ease of data synthesis and critical analysis. Meta-analysis was performed where there were sufficient studies. Maternal blood pressure (BP) and total vascular resistance (TVR) were increased in prone (sBP 109 vs 104 mmHg, p = 0.03; dBP 74 vs 67 mmHg, p = 0.003; TVR 1302 vs 1075 dyne.s-1cm-5, p = 0.03). CO was reduced in prone (5.7 vs 7.1 mL/minute, p = 0.003). Fetal heart rate, variability and decelerations were unaltered. However, fetal accelerations were less common in prone position (86% vs 95%, p = 0.03). Anxiety was reduced after the procedure, compared to beforehand (p = 0.002), despite a marginal decline in comfort (p = 0.04).The model predicted that if occlusion of the inferior vena cava occurred, the sBP, dBP and CO would generally decrease. However, the TVR remained relatively consistent, which implies that the MAP and CO decrease at a similar rate when occlusion occurs. The scoping review found that maternal and fetal outcomes from 47 included case reports of prone positioning during pregnancy were generally favourable. Meta-analysis of three prospective studies investigating maternal haemodynamic effects of prone position found an increase in sBP and maternal heart rate, but no effect on respiratory rate, oxygen saturation or baseline fetal heart rate (though there was significant heterogeneity between studies). Prone position was associated with a reduction in CO but an uncertain effect on fetal wellbeing. The decline in CO may be due to caval compression, as supported by the computational model. Further work is needed to optimise the safety of prone positioning in pregnancy. This trial was registered at clinicaltrials.gov (NCT04586283).

Three categories of similarities between the placenta and cancer that can aid cancer treatment: Cells, the microenvironment, and metabolites.

Cancer is one of the most harmful diseases, while pregnancy is a common condition of females. Placenta is the most important organ for fetal growth, which has not been fully understand. It's well known that placenta and solid tumor have some similar biological behaviors. What's more, decidua, the microenvironment of placenta, and metabolism all undergo adaptive shift for healthy pregnancy. Interestingly, decidua and the tumor microenvironment (TME); metabolism changes during pregnancy and cancer cachexia all have underlying links. However, whether the close link between pregnancy and cancer can bring some new ideas to treat cancer is still unclear. So, in this review we note that pregnancy may offer clues to treat cancer related to three categories: from cell perspective, through the shared development process of the placenta and cancer; from microenvironment perspective, though the shared features of the decidua and TME; and from metabolism perspective, through shared metabolites changes during pregnancy and cancer cachexia. Firstly, comparing gene mutations of both placenta and cancer, which is the underlying mechanism of many similar biological behaviors, helps us understand the origin of cancer and find the key factors to restore tumorigenesis. Secondly, exploring how decidua affect placenta development and similarities of decidua and TME is helpful to reshape TME, then to inhibit cancer. Thirdly, we also illustrate the possibility that the altered metabolites during pregnancy may reverse cancer cachexia. So, some key molecules changed in circulation of pregnancy may help relieve cachexia and make survival with cancer realized.

The Effect of Physical Exercise on Oxidation Capacity and Utero-Placental Circulation in Pregnancies with Gestational Diabetes Mellitus and Uncomplicated Pregnancies, a Pilot Study.

Background: Gestational diabetes mellitus (GDM) is associated with aggravated oxidation capacity and utero-placental circulation, while aerobic exercise could improve both. The study aims to assess oxidation capacity and utero-placental circulation before and after a bout of aerobic exercise in GDM and uncomplicated pregnancies.; Methods: In this cross-sectional study, women with GDM (GDMs) and women with uncomplicated pregnancies(controls), underwent 30 min of moderate intensity cycling. Total antioxidant capacity (TAC), catalase activity (CAT), reduced glutathione (GSH), Uterine Arteries (UtA PI) and Umbilical Artery (UmA PI) pulsatility indexes were estimated prior-to, immediately after and one hour after exercise; Results: In each group, 25 pregnant women were included. In both groups, between prior-to and immediately after exercise, TAC and CAT increased, while GSH decreased, (p < 0.001). In GDMs, CAT was lower than controls at any time point (p < 0.05), while in GDMs delta(Δ) CAT (prior-to and immediately after exercise) was lower than controls (p = 0.003). In GDMs, UtA PI centiles decreased between prior-to and either immediately or one hour after exercise, while they did not change in controls. In GDMs, pre-conceptional BMI and weight gain predicted negatively ΔTAC (prior-to to one hour after exercise); Conclusions: Moderate intensity exercise bout improves oxidation capacity in GDM and uncomplicated pregnancies, although at a lesser extent in the former. Exercise leads to decreased UtA arteries resistance in women with GDM.

Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus†.

Bone marrow-derived progenitor cells (BMDPCs) are mobilized to the circulation in pregnancy and get recruited to the pregnant decidua where they contribute functionally to decidualization and successful implantation. However, the molecular mechanisms underlying BMDPCs recruitment to the decidua are unknown. CXCL12 ligand and its CXCR4 receptor play crucial roles in the mobilization and homing of stem/progenitor cells to various tissues. To investigate the role of CXCL12-CXCR4 axis in BMDPCs recruitment to decidua, we created transgenic GFP mice harboring CXCR4 gene susceptible to tamoxifen-inducible Cre-mediated ablation. These mice served as BM donors into wild-type C57BL/6J female recipients using a 5-fluorouracil-based nongonadotoxic submyeloablation to achieve BM-specific CXCR4 knockout (CXCR4KO). Successful CXCR4 ablation was confirmed by RT-PCR and in vitro cell migration assays. Flow cytometry and immunohistochemistry showed a significant increase in GFP+ BM-derived cells (BMDCs) in the implantation site as compared to the nonpregnant uterus of control (2.7-fold) and CXCR4KO (1.8-fold) mice. This increase was uterus-specific and was not observed in other organs. This pregnancy-induced increase occurred in both hematopoietic (CD45+) and nonhematopoietic (CD45-) uterine BMDCs in control mice. In contrast, in CXCR4KO mice there was no increase in nonhematopoietic BMDCs in the pregnant uterus. Moreover, decidual recruitment of myeloid cells but not NK cells was diminished by BM CXCR4 deletion. Immunofluorescence showed the presence of nonhematopoietic GFP+ cells that were negative for CD45 (panleukocyte) and DBA (NK) markers in control but not CXCR4KO decidua. In conclusion, we report that CXCR4 expression in nonhematopoietic BMDPCs is essential for their recruitment to the pregnant decidua.

Preterm Birth Associates With Increased Placental Expression of MDR Transporters Irrespective of Prepregnancy BMI.

Preterm birth (PTB) and suboptimal prepregnancy body mass index (BMI) operate through inflammatory pathways to impair fetoplacental development. Placental efflux transporters mediate fetal protection and nutrition; however, few studies consider the effect of both PTB and BMI on fetal protection. We hypothesized that PTB would alter the expression of placental multidrug resistance (MDR) transporters and selected proinflammatory cytokines, and that maternal underweight and obesity would further impair placental phenotype. To determine whether placental MDR transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and proinflammatory cytokine levels are altered by PTB and maternal BMI. A cross-sectional study was conducted to assess the effect of PTB (with/without chorioamnionitis), or the effect of maternal prepregnancy BMI on placental MDR transporter and interleukin (IL)-6 and -8 expression in 60 preterm and 36 term pregnancies. ABCB1 expression was increased in preterm compared to term placentae (P = .04). P-gp (P = .008) and BCRP (P = .01) immunolabeling was increased among all preterm compared to term placentae, with P-gp expression further increased in preterm pregnancies with chorioamnionitis (PTC, P = .007). Placental IL-6 mRNA expression was decreased in PTC compared to term placentae (P = .0005) and PTC associated with the greatest proportion of anti-inflammatory medications administered during pregnancy. Maternal BMI group did not influence placental outcomes. PTB and infection, but not prepregnancy BMI, alter placental expression of MDR transporters and IL-6. This may have implications for fetal exposure to xenobiotics that may be present in the maternal circulation in pregnancies complicated by PTB.

P-025. Comparison of methods for determining PlGF and sFlt-1 levels in maternal circulation in pregnancies complicated by placental dysfunction

P-025. Comparison of methods for determining PlGF and sFlt-1 levels in maternal circulation in pregnancies complicated by placental dysfunction

Colour Doppler study of Fetomaternal and uteroplacental circulation in pregnancy induced hypertension and/or oligohydramnios

Purpose: To study the fetoplacental and uteroplacental circulation by evaluating uterine artery, umbilical artery and fetal MCA using color Doppler in hypertensive disorders of pregnancy and oligohydramnios in second and third trimester with comparing different parameters.Methodology: Total 62 antenatal patients in their second or third trimester, who were clinically diagnosed as having pregnancy-induced hypertension or oligohydramnios by department of obstetrics had been recruited. Color Doppler study of umbilical artery, uterine artery and fetal MCA was performed with measurement of umbilical artery PI and SV/DV ratio, MCA PI and SV/DV ratio, uterine artery RI and SV/DV ratio and CPR.At last, color Doppler prediction was correlated with fetal outcome.Results: Out of 62 patients, 27 had PIH, 14 had associated oligohydramnios with PIH and 21 had oligohydramnios. 56% patients with PIH and 47% patients with oligohydramnios had adverse fetal outcome. The percentages of abnormal parameters of uterine artery, umbilical artery and MCA in PIH patients were 61%, 46% and 51% respectively. The sensitivity and specificity for detecting fetal distress was 70% and 81%, 70% and 87% and 67% and 86% for uterine artery, umbilical artery and fetal MCA respectively. CPR was 100% sensitive and 92.3% specific in detecting severe fetal distress.Conclusion: Chances of fetal compromise inutero are high in PIH patients, also significant number of oligohydramnios patients show adverse fetal outcome. Color Doppler study of fetoplacental and uteroplacental circulation proved a useful and noninvasive technique in determining hypoxic fetus and planning timely management of delivery before severe hypoxic injury to fetus occurs. Uterine artery and umbilical artery are more sensitive followed by MCA in diagnosing fetal distress.

Circulating Micro particles: a Risk Factorfor Recurrent Abortion in Women at theUniversity Teaching Hospital, Lusaka,Zambia

Background: Circulating micro particles are minute particles associated with prothrombotic nature found to be increased in the uteroplacental circulation in pregnancy, as such micro particles may be directly or indirectly associated with pregnancy loss. With abortion cases accounting for approximately 80% of cases at the Obstetrics and Gynaecology emergency ward at The University Teaching Hospital, this study aimed to determine if circulating micro particles are associated with the risk of recurrent abortion. Methods: A case-control study enrolled 18 women with two or more recurrent abortions and 55 parous women as controls. After counselling performed by a trained mid-wife, a blood sample was collected in a citrated container and platelet poor plasma isolated. Micro particles were measured by flow cytometry using fluorescent annexin V-fluorescence isothiocyanate conjugate. Results: Increased micro particle levels was defined as more than 2 standard deviation above the mean of controls. The mean found was 202/μl in 4 of the 18 women with recurrent abortions (22%), as opposed to 2 of the 55 parous women (4%), t(20)=2.49, P=0.022, 95% CI 182.20-16.09. Conclusions: The increased micro particles levels in women with recurrent abortions supports emerging evidence that micro particles have a role to play in abortion.

Fetal Growth and Fetoplacental Circulation in Pregnancies Following Bariatric Surgery: A Prospective Study

(BJOG. 2020;127:839–846) Nearly one third of the population within the United States and one fourth of the population of the UK can be classified as obese, which includes one quarter of all reproductive-aged women. There are significant short-term and long-term adverse outcomes for both baby and mother associated with pregnancy while obese. Obese mothers exhibit a higher propensity for gestational diabetes mellitus, preeclampsia, cesarean delivery, or postpartum hemorrhage, as well as the development of cardiovascular disease and type 2 diabetes later in life. In addition to macrosomia, children of obese mothers are more likely to develop type 2 diabetes and cardiovascular disease in adulthood. Bariatric surgery, an effective weight-reduction treatment, is becoming more common for women of childbearing age. This study aimed to investigate the intrauterine fetal growth pattern and placental function, in postbariatric pregnancies as compared with patients of no history of maternal weight-loss surgery.

The Importance of Doppler Analysis of Uterine Circulation in Pregnancy for a Better Understanding of Preeclampsia.

Background:The etiology of preeclampsia has still not been completely explained. Early identification of women with the risk of developing preeclampsia is a key goal of antenatal care.Objective:To investigate risk factors for preeclampsia from the history, laboratory and ultrasound findings (Doppler).Methods:Pregnant women with normal Doppler sonography in the second trimester of pregnancy were classified as a control group, while pregnant women with impaired Doppler in the second trimester were considered as the investigated group with presumably increased risk for preeclampsia. A total number of 80 patients was included in the study (40 patients in each group).Results:The difference of urea, uric acid and lactate dehydrogenase (LDH) in the serum of the control and investigated group was statistically significant, while the differences were not statistically significant for creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The presence of a notch sign during assessment of blood flow in uterine arteries in subjects in the investigated group with the diagnosis of preeclampsia had the specificity of 47.62%, and sensitivity of 88.89%. The positive predictive value of a notch sign during assessment of blood flow in uterine arteries as a marker for diagnosis of preeclampsia in the second trimester of pregnancy was 90.91%, and its negative. Systolic and diastolic blood pressure are dependent variables which are predicting preeclampsia, whilst a notch sign in uterine arteries was designated as an independent variable predicting preeclampsia.Conclusion:From the laboratory tests the following parameters were considered as the risk factors for preeclampsia: increasing levels of urea, uric acid, and LDH. Notch sign was considered to be a very strong predictor of preeclampsia, especially if present bilaterally. Doppler sonography in the second trimester of pregnancy is a good predictor for early diagnosis of preeclampsia.

Clinical implications of dexamethasone administration on Doppler indices of umbilical and middle cerebral arteries in preterm fetuses

BackgroundMaternal administration of dexamethasone is essential to improve fetal lung surfactant production and hasten the fetal lung maturity in women at risk for preterm birth. Umbilical and fetal middle cerebral arteries' (MCAs) Doppler indices are important to evaluate the effects of dexamethason on fetal and uteroplacental circulation in pregnancies at risk for preterm birth.ObjectiveThe aim was to evaluate the effects of maternal dexamethasone administration on umbilical and fetal MCAs Doppler indices (Resistance index (RI), Pulsalitility index (PI), and S/D ratio) in singleton pregnancies considered at risk for preterm delivery.Patients and methodsA total of 100 women were included in this study. They were at risk of preterm labor and were divided in two groups: 50 participants who took dexamethasone as a study group and 50 participants did not take dexamethasone as a control group. Doppler examination of umbilical and MCAs was performed, and comparisons between values of study group and control group were done after 0, 1, 4, and 7 weeks of dexamethasone administration.ResultsThe authors found a significant change in the mean values of the pulsatility and resistive indices and systolic-diastolic ratios of study group in umbilical artery and fetal MCA after 1 week after dexamethasone administration.ConclusionAdministration of dexamethasone improves Doppler indices and biophysical profile and decreases NICU admission. In healthy fetuses, a transient, significant, and unexplained decrease in fetal MCA impedance occurs on the fourth day following maternal dexamethasone administration.

Fetal growth and fetoplacental circulation in pregnancies following bariatric surgery: a prospective study.

To investigate the intrauterine fetal growth pattern and fetoplacental circulation in pregnancies following bariatric surgery. Prospective study. Maternity Unit, UK. One hundred and sixty-two pregnant women; 54 with previous bariatric surgery and 108 with no surgery but similar booking body mass index. Participants were seen at 11-14, 20-24, 30-33 and 35-37weeks of gestation and an oral glucose tolerance test (OGTT) was performed at 27-30weeks. Fetal head and abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW) and fetoplacental Dopplers were measured at three time-points in pregnancy. Birthweight (BW) was recorded. Variables were modelled after adjustment for maternal/pregnancy characteristics. Model estimates are reported as posterior means and quantile-based 90% credible intervals (CrI). Fetal biometry, fetoplacental Doppler, BW. Compared with the no surgery group, the post-bariatric surgery group had lower EFW during gestation (up to -120g; [-189g, -51g] lighter) at 35-37weeks, with smaller AC and FL. Similarly, infants of mothers with previous bariatric surgery had lower average BW [-202g [-330g, -72g] lighter). Overall, there was no difference in the fetoplacental Doppler indices between groups but maternal glucose levels at OGTT were positively correlated with third-trimester EFW and BW. Fetuses of women with previous bariatric surgery are smaller during pregnancy and at birth, compared with those of women without such surgery, and this may be related to the lower maternal glucose levels seen in the former population. The fetoplacental circulation appears not to be altered by maternal weight loss surgery. Offspring of post-bariatric women are smaller during pregnancy and at birth but this is not due to placental insufficiency.

Association between the fetal cerebroplacental ratio and biomarkers of hypoxia and angiogenesis in the maternal circulation at term

ObjectivesA low fetal cerebroplacental ratio (CPR) in late pregnancy is a marker of a fetus that has failed to reach its growth potential and is associated with a variety of perinatal and pregnancy complications. It is not known if it is also correlated with aberrations in angiogenic, hypoxia-responsive or inflammatory cytokine levels in the maternal circulation. We investigated if there were any differences in levels of biomarkers of angiogenesis, endothelial cell dysfunction, hypoxia and/or inflammation in term pregnancies with a low fetal CPR compared to controls. We hypothesized that as the CPR is a marker of suboptimal growth, this would be reflected in a shift towards upregulation of hypoxia-responsive factors even in non-small for gestational age fetuses. Study designWe used Multiplex ELISA to measure a panel of 28 candidate biomarkers of angiogenesis and/or hypoxia in pre-labour maternal plasma from 113 women at term, stratified for CPR <10th centile vs. CPR >10th centile. Plasma levels of the biomarkers were measured using 2 multiplex Luminex assays - a commercially available human angiogenesis/growth factor panel (R&D Systems®), comprising 15 analytes and an in-house custom panel of a further 13 candidate biomarkers. ResultsOf the 28 candidate biomarkers investigated, we found significantly elevated levels of Carbonic Anhydrase 9 and soluble Fms-like tyrosine kinase (Vascular Endothelial Growth Factor Receptor 1), and lower levels of Placental Growth Factor in plasma from women with a low fetal CPR. The soluble Fms-like tyrosine kinase-1/Placental Growth Factor ratio was also markedly elevated in this cohort. We also demonstrated significant inverse correlations between the fetal CPR and Carbonic Anydrase 9, soluble Fms-like tyrosine kinase and Hepatocyte Growth Factor. ConclusionsA low fetal CPR is associated with changes in some hypoxia-responsive and angiogenesis factors in the maternal circulation in pregnancies with normally grown fetuses.

Investigating Maternal Brain Alterations in Preeclampsia: the Need for a Multidisciplinary Effort

To provide insight into the mechanisms underlying cerebral pathophysiology and to highlight possible methods for evaluation, screening, and surveillance of cerebral complications in preeclampsia. The pathophysiology of eclampsia remains enigmatic. Animal studies show that the cerebral circulation in pregnancy and preeclampsia might be affected with increased permeability over the blood-brain barrier and altered cerebral blood flow due to impaired cerebral autoregulation. The increased blood pressure cannot be the only underlying cause of eclampsia and cerebral edema, since some cases of eclampsia arise without simultaneous hypertension. Findings from animal studies need to be confirmed in human tissues. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Cerebral complications of preeclampsia are significant factors in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend an international and multidisciplinary effort not only to overcome the issue of limited sample availability but also to optimize the quality of research.

Placental Syncytiotrophoblast-Derived Extracellular Vesicles Carry Active NEP (Neprilysin) and Are Increased in Preeclampsia.

NEP (neprilysin) is a widely expressed membrane-bound metalloprotease, which binds and cleaves a variety of peptides including vasodilators, natriuretics, and diuretics. Higher levels of NEP result in hypertension-a cardinal feature of the placental disease preeclampsia. Syncytiotrophoblast-derived extracellular vesicles (EVs), comprising microvesicles and exosomes, are released into the peripheral circulation in pregnancy and are postulated as a key mechanism coupling placental dysfunction and maternal phenotype in preeclampsia. We aimed to determine whether higher levels of active NEP are found in syncytiotrophoblast-derived EVs in preeclampsia compared with normal pregnancy. Using immunostaining and Western blotting, we first demonstrated that NEP levels are greater not only in preeclampsia placental tissue but also in syncytiotrophoblast-derived microvesicles and exosomes isolated from preeclampsia placentas ( P<0.05, n=5). We confirmed placental origin using antibody-coated magnetic beads to isolate NEP-bound vesicles, finding that they stain for placental alkaline phosphatase. NEP on syncytiotrophoblast-derived EVs is active and inhibited by thiorphan ( P<0.01, n=3; specific inhibitor). Syncytiotrophoblast-derived microvesicles, isolated from peripheral plasma, demonstrated higher NEP expression in preeclampsia using flow cytometry ( P<0.05, n=8). We isolated plasma exosomes using size-exclusion chromatography and showed greater NEP activity in preeclampsia ( P<0.05, n=8). These findings show that the placenta releases active NEP into the maternal circulation on syncytiotrophoblast-derived EVs, at significantly greater levels in preeclampsia. NEP has pathological roles in hypertension, heart failure, and amyloid deposition, all of which are features of preeclampsia. Circulating syncytiotrophoblast-derived EV-bound NEP thus may contribute to the pathogenesis of this disease.

OC24.05: The interaction between the maternal systemic and uteroplacental circulations in pregnancies resulting in small‐for‐gestational‐age newborns

OC24.05: The interaction between the maternal systemic and uteroplacental circulations in pregnancies resulting in small‐for‐gestational‐age newborns

296. Loss of Placental NR4A2 may contribute to the pathogeneisis of pre-eclampsia

Introduction Placental dysfunction is a key contributor in the development of pre-eclampsia. Recently, we identified NR4A2 mRNA to be altered in the maternal circulation in pregnancies complicated by severe, early onset fetal growth restriction and pre-eclampsia (PE). Objective The current study aimed to determine whether NR4A2 expression was altered in the human placenta with hypoxic insult and pre-eclampsia. Methods Isolated primary cytotrophoblasts (n = 5) and placental explant tissue (n = 4) from normal term placentas were cultured under normoxia (8% oxygen) and hypoxia (1% oxygen) for 24 h. Expression of NR4A2 was assessed by qPCR. Placental tissue was collected from severe early onset PE (n = 49) and gestation matched controls (n = 47) to test NR4A2 mRNA expression. NR4A2 protein was assessed in PE (n = 31) and preterm (n = 22) placenta by Western blotting. Primary cytotrophoblasts were transfected with NR4A2 siRNA (n = 3) to silence gene expression (under normoxia and hypoxia for 48 h). sFLT-1 secretion was assessed by ELISA and expression of the sFLT-1 variants (e15a and i13) and cell survival associated genes by qPCR. Normality (Gaussian distribution) was assessed in each case and appropriate post hoc analysis was performed. Results NR4A2 mRNA expression was significantly reduced with hypoxia in trophoblast, but not placental explants. Additionally, NR4A2 mRNA expression was significantly reduced in PE placenta. However, there was no difference in NR4A2 protein expression between PE and controls. Silencing NR4A2 significantly increased anti-angiogenic factor sFLT-1 secretion, but not sFLT-1 mRNA expression. Furthermore, loss of NR4A2 in the trophoblast reduced pro-survival IGF2 gene expression and increased NOX4 (oxidative stress marker) expression. Conclusion NR4A2 is reduced in the trophoblast with hypoxia and mRNA expression is low in the PE placenta. Signs of placental dysfunction were observed with the silencing of NR4A2 in the trophoblast and an increase in sFLT-1 secretion suggests potential roles for NR4A2 in the pathogenesis of PE.

Impaired vasocontractile responses to adenosine in chorionic vessels of human term placenta from pregnant women with pre-existing and gestational diabetes

There is clinical and experimental evidence for altered adenosine signalling in the fetoplacental circulation in pregnancies complicated by diabetes, leading to adenosine accumulation in the placenta. However, the consequence for fetoplacental vasocontractility is unclear. This study examined contractility to adenosine of chorionic vessels from type 1 diabetes mellitus, gestational diabetes mellitus and normal pregnancies. Chorionic arteries and veins were isolated from human placenta from normal, gestational diabetes mellitus and type 1 diabetes mellitus pregnancies. Isometric tension recording measured responses to adenosine and the thromboxane A2 analogue U46619 (thromboxane A2 mediates fetoplacental vasoconstriction to adenosine). Adenosine and thromboxane prostanoid receptor protein expression was determined by immunoblotting. Adenosine elicited contractions in chorionic arteries and veins which were impaired in both gestational diabetes mellitus and type 1 diabetes mellitus. Contractions to potassium chloride were unchanged. Adenosine A2A and A2B receptor protein levels were not different in gestational diabetes mellitus and normal pregnancies. Contractions to U46619 were unaltered in gestational diabetes mellitus arteries and increased in type 1 diabetes mellitus arteries. Overnight storage of vessels restored contractility to adenosine in gestational diabetes mellitus arteries and normalized contraction to U46619 in type 1 diabetes mellitus arteries. These data are consistent with the concept of aberrant adenosine signalling in diabetes; they show for the first time that this involves impaired adenosine contractility of the fetoplacental vasculature.

Antenatal dexamethasone effect on Doppler blood flow velocity in women at risk for preterm birth: prospective case series.

Maternal administration of corticosteroids is essential to improve fetal lung surfactant production and hasten the fetal lung maturity in women at risk for preterm birth. The current study aims to evaluate the effects of dexamethasone on fetal and uteroplacental circulation in pregnancies at risk for preterm birth after 24 hours of its administration. A prospective cross-sectional study was carried out in a tertiary University Hospital and included 52 pregnant women with singleton pregnancies. Doppler studies were performed on maternal uterine arteries, umbilical artery, fetal middle cerebral artery (MCA) and fetal descending aorta and just before dexamethasone administration and repeated 24 hours after completion of the course. There was a statistically significant difference between all Doppler indices in the umbilical artery (PI= 1.09±0.4 and 1.05±0.39, RI= 0.66±0.14 and 0.63±0.14; p=0.001), fetal MCA (RI= 0.86±0.12 and 0.83±0.13, PI= 2.19±0.72 and 2.15±0.72; p=0.001) and aorta (RI= 0.9±0.55 and 0.87±0.55; p=0.001, PI= 1.91±0.44 and 1.89±0.44; p=0.040) in comparison before and 24 hours after maternal dexamethasone administration respectively. Also uterine artery PI was significantly different (0.9±0.27 and 0.87±0.26; p=0.001). Antenatal dexamethasone for women at risk of preterm birth improves the fetal and uteroplacental blood flow at 24 hours after its administration.