Ganesh Acharya

Differential placental gene expression in severe preeclampsia.

We investigated the global placental gene expression profile in severe preeclampsia. Twenty-one women were randomly selected from 50 participants with uncomplicated pregnancies to match 21 patients with severe preeclampsia. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate the gene expression profile. After RNA isolation, five preeclamptic placentas were excluded due to poor RNA quality. The series composed of 37 hybridizations in a one-channel detection system of chemiluminescence emitted by the microarrays. An empirical Bayes analysis was applied to find differentially expressed genes. In preeclamptic placentas 213 genes were significantly (fold-change>or=2 and p<or=0.01) up-regulated and 82 were down-regulated, compared with normal placentas. Leptin (40 fold), laeverin (10 fold), different isoforms of beta-hCG (3-6 fold), endoglin (4 fold), FLT1 (3 fold) and FLT4 (2 fold) were up-regulated. PDGFD was down-regulated (2 fold). Several differentially expressed genes were associated with Alzheimer disease, angiogenesis, Notch-, TGFbeta- and VEGF-signalling pathways. Sixteen genes best discriminated preeclamptic from normal placentas. Comparison between early- (<34 weeks) and late-onset preeclampsia showed 168 differentially expressed genes with oxidative stress, inflammation, and endothelin signalling pathways mainly involved in early-onset disease. Validation of the microarray results was performed by RT-PCR, quantitative urine hCG measurement and placental histopathologic examination. In summary, placental gene expression is altered in preeclampsia and we provide a comprehensive list of the differentially expressed genes. Placental gene expression is different between early- and late-onset preeclampsia, suggesting differences in pathophysiology.

ISUOG Practice Guidelines : use of Doppler ultrasonography in obstetrics

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, teaching and research related to diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. They are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

Reference ranges for serial measurements of blood velocity and pulsatility index at the intra‐abdominal portion, and fetal and placental ends of the umbilical artery

To construct reference ranges for serial measurements of umbilical artery (UA) blood flow velocity and pulsatility index (PI) at standardized insonation sites during the second half of pregnancy.

Major congenital heart disease in Northern Norway: shortcomings of pre- and postnatal diagnosis.

Background.  Congenital heart disease (CHD) is a significant cause of perinatal mortality and morbidity worldwide. Prenatal detection rate of CHD remains low in most European countries and a substantial proportion of infants with serious heart disease are diagnosed only after discharge from hospital after birth. Earlier recognition of treatable abnormalities may improve the perinatal outcome. The purpose of this study was to evaluate the incidence, pre‐ and postnatal diagnosis and outcome of major CHD in two northern‐most counties of Norway.

A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy

Please cite this paper as: Flo K, Wilsgaard T, Vårtun Å, Acharya G. A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy. BJOG 2010;117:837–844.

Experimental validation of uterine artery volume blood flow measurement by Doppler ultrasonography in pregnant sheep

To test the hypothesis that Doppler‐derived (calculated) uterine artery volume blood flow (cQUtA) reflects accurately volume blood flow measured directly (mQUtA) in an experimental setting.

Comparison between pulsed‐wave Doppler‐ and tissue Doppler‐derived Tei indices in fetuses with and without congenital heart disease

The aim of this study was to compare the right (RV) and left (LV) ventricular Tei indices obtained by pulsed‐wave Doppler (PD) and tissue Doppler (TD) methods in fetuses with structurally normal and abnormal hearts.

Folate rescues lithium-, homocysteine- and Wnt3A-induced vertebrate cardiac anomalies.

SUMMARY Elevated plasma homocysteine (HCy), which results from folate (folic acid, FA) deficiency, and the mood-stabilizing drug lithium (Li) are both linked to the induction of human congenital heart and neural tube defects. We demonstrated previously that acute administration of Li to pregnant mice on embryonic day (E)6.75 induced cardiac valve defects by potentiating Wnt–β-catenin signaling. We hypothesized that HCy may similarly induce cardiac defects during gastrulation by targeting the Wnt–β-catenin pathway. Because dietary FA supplementation protects from neural tube defects, we sought to determine whether FA also protects the embryonic heart from Li- or HCy-induced birth defects and whether the protection occurs by impacting Wnt signaling. Maternal elevation of HCy or Li on E6.75 induced defective heart and placental function on E15.5, as identified non-invasively using echocardiography. This functional analysis of HCy-exposed mouse hearts revealed defects in tricuspid and semilunar valves, together with altered myocardial thickness. A smaller embryo and placental size was observed in the treated groups. FA supplementation ameliorates the observed developmental errors in the Li- or HCy-exposed mouse embryos and normalized heart function. Molecular analysis of gene expression within the avian cardiogenic crescent determined that Li, HCy or Wnt3A suppress Wnt-modulated Hex (also known as Hhex) and Islet-1 (also known as Isl1) expression, and that FA protects from the gene misexpression that is induced by all three factors. Furthermore, myoinositol with FA synergistically enhances the protective effect. Although the specific molecular epigenetic control mechanisms remain to be defined, it appears that Li or HCy induction and FA protection of cardiac defects involve intimate control of the canonical Wnt pathway at a crucial time preceding, and during, early heart organogenesis.

Role of routine ultrasonography in monitoring the outcome of medical abortion in a clinical setting

Background.  Clinical methods generally used to evaluate the completeness of medical abortion are not accurate. There are no published reports evaluating the role of routine ultrasonography in monitoring the outcome of medical abortion. The purpose of this study was to investigate whether routine transvaginal ultrasonography (TVS) at the follow‐up visit after medical abortion can accurately identify women who will require surgical intervention.

Differences in gene expression between first and third trimester human placenta : a microarray study.

Background The human placenta is a rapidly developing organ that undergoes structural and functional changes throughout the pregnancy. Our objectives were to investigate the differences in global gene expression profile, the expression of imprinted genes and the effect of smoking in first and third trimester normal human placentas. Materials and Methods Placental samples were collected from 21 women with uncomplicated pregnancies delivered at term and 16 healthy women undergoing termination of pregnancy at 9–12 weeks gestation. Placental gene expression profile was evaluated by Human Genome Survey Microarray v.2.0 (Applied Biosystems) and real-time polymerase chain reaction. Results Almost 25% of the genes spotted on the array (n = 7519) were differentially expressed between first and third trimester placentas. Genes regulating biological processes involved in cell proliferation, cell differentiation and angiogenesis were up-regulated in the first trimester; whereas cell surface receptor mediated signal transduction, G-protein mediated signalling, ion transport, neuronal activities and chemosensory perception were up-regulated in the third trimester. Pathway analysis showed that brain and placenta might share common developmental routes. Principal component analysis based on the expression of 17 imprinted genes showed a clear separation of first and third trimester placentas, indicating that epigenetic modifications occur throughout pregnancy. In smokers, a set of genes encoding oxidoreductases were differentially expressed in both trimesters. Conclusions Differences in global gene expression profile between first and third trimester human placenta reflect temporal changes in placental structure and function. Epigenetic rearrangements in the human placenta seem to occur across gestation, indicating the importance of environmental influence in the developing feto-placental unit.