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Fetal compromise of uteroplacental blood flow leads to utero-placental insufficiency. This study aimed to find a correlation between serum biomarkers from Quadriple test and fetoplacental unit, in the second trimester of pregnancy, as possible predictors for the adverse perinatal outcome. Material and method: This cohort study was conducted in a SHOG “Mother Theresa”, Skopje, from November 2019 to June 2021. It includes 673 second trimester pregnant women, followed up and monitored till delivery. Results: From 673 respondents, 523 that is 77.7% made up the control group, while 150 that is 22.3% of pregnant women made up the examined group. From the examined group, 48 (7.13%) had preeclampsia, 32 (4.75%) had pregnancy-induced hypertension, 20 (2.97%) had a small fetus for gestational age, and 50 (7.43%) had intrauterine growth retardation. Discussion: high values of Inhibin A in pregnant women with adverse outcome, statistically was confirmed as significant, while HCG values were significantly higher in group with preeclampsia. Pregnant women with preeclampsia significantly more often than pregnant women from control group had higher values of serum AFP, and it wasn’t found significantly statistical difference in medial values of unconjugated Estriol in four examined groups compared to control group. It was confirmed the hypothesis that the placental volume by screening in second trimester is important for pregnancy outcome, as well as the flows in uterine and umbilical arteries. Conclusion: Inhibin A value as a single marker for adverse pregnancy outcome was the best predictor, while the combination of biomarkers from Quadriple test and the uterine arteries flow in the second trimester of pregnancy, represents the best differentiating ability test for pregnant women for adverse and favorable pregnancy outcome. [ABSTRACT FROM AUTHOR]

Key points: Human placental function is evaluated using non‐invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption (VO2) is only possible during Caesarean delivery.This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and VO2 by the gravid uterus, uteroplacenta and fetus.Normal late gestational human uteroplacental VO2 by MRI was ∼4 ml min−1 kg−1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques.Our MRI approach can quantify uteroplacental VO2, which involves the quantification of maternal‐ and fetal‐placental blood flows, fetal oxygen delivery and VO2, and the oxygen gradient between uterine‐ and umbilical‐venous blood, providing a comprehensive assessment of placental function with clinical potential. It has not been feasible to perform routine clinical measurement of human placental oxygen consumption (VO2) and in vitro studies do not reflect true metabolism in utero. Here we propose an MRI method to non‐invasively quantify in utero placental and fetal oxygen delivery (DO2) and VO2 in healthy humans and sheep. Women (n = 20) and Merino sheep (n = 10; 23 sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36 ± 2 weeks and 128 ± 9 days, respectively; mean ± SD). Blood flow (phase‐contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine‐ and umbilical‐placental vessels, allowing calculation of uteroplacental and fetal DO2 and VO2. Maternal DO2 (ml min−1 kg−1 fetus) to the gravid uterus was similar in humans and sheep (human = 54 ± 15, sheep = 53 ± 21, P = 0.854), while fetal DO2 (human = 25 ± 4, sheep = 22 ± 5, P = 0.049) was slightly lower in sheep. Uteroplacental and fetal VO2 (ml min−1 kg−1 fetus; uteroplacental: human = 4.1 ± 1.5, sheep = 3.5 ± 1.9, P = 0.281; fetus: human = 6.8 ± 1.3, sheep = 7.2 ± 1.7, P = 0.426) were similar between species. Late gestational uteroplacental:fetal VO2 ratio did not change with age (human, P = 0.256; sheep, P = 0.121). Human umbilical blood flow (ml min−1 kg−1 fetus) decreased with advancing age (P = 0.008), while fetal VO2 was preserved through an increase in oxygen extraction (P = 0.046). By contrast, sheep fetal VO2 was preserved through stable umbilical flow (ml min−1 kg−1; P = 0.443) and oxygen extraction (P = 0.582). MRI derived measurements of uteroplacental and fetal VO2 between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical 'placental function test'. Key points: Human placental function is evaluated using non‐invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption (VO2) is only possible during Caesarean delivery.This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and VO2 by the gravid uterus, uteroplacenta and fetus.Normal late gestational human uteroplacental VO2 by MRI was ∼4 ml min−1 kg−1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques.Our MRI approach can quantify uteroplacental VO2, which involves the quantification of maternal‐ and fetal‐placental blood flows, fetal oxygen delivery and VO2, and the oxygen gradient between uterine‐ and umbilical‐venous blood, providing a comprehensive assessment of placental function with clinical potential. [ABSTRACT FROM AUTHOR]

Background: The amniotic fluid (AF) cell-free transcriptome is modulated by physiologic and pathologic processes during pregnancy. AF gene expression changes with advancing gestation reflect fetal development and organ maturation; yet, defining normal expression and splicing patterns for biomarker discovery in obstetrics requires larger heterogeneous cohorts, evaluation of potential confounding factors, and novel analytical approaches. Methods: Women with a normal pregnancy who had an AF sample collected during midtrimester (n = 30) or at term gestation (n = 68) were included. Expression profiling at exon level resolution was performed using Human Transcriptome Arrays. Differential expression was based on moderated t-test adjusted p < 0.05 and fold change > 1.25; for differential splicing, a splicing index > 2 and adjusted p < 0.05 were required. Functional profiling was used to interpret differentially expressed or spliced genes. The expression of tissue-specific and cell-type specific signatures defined by single-cell genomics was quantified and correlated with covariates. In-silico validation studies were performed using publicly available datasets. Results: 1) 64,071 genes were detected in AF, with 11% of the coding and 6% of the non-coding genes being differentially expressed between midtrimester and term gestation. Expression changes were highly correlated with those previously reported (R > 0.79, p < 0.001) and featured increased expression of genes specific to the trachea, salivary glands, and lung and decreased expression of genes specific to the cardiac myocytes, uterus, and fetal liver, among others. 2) Single-cell RNA-seq signatures of the cytotrophoblast, Hofbauer cells, erythrocytes, monocytes, T and B cells, among others, showed complex patterns of modulation with gestation (adjusted p < 0.05). 3) In 17% of the genes detected, we found differential splicing with advancing gestation in genes related to brain development processes and immunity pathways, including some that were missed based on differential expression analysis alone. Conclusions: This represents the largest AF transcriptomics study in normal pregnancy, reporting for the first time that single-cell genomic signatures can be tracked in the AF and display complex patterns of expression during gestation. We also demonstrate a role for alternative splicing in tissue-identity acquisition, organ development, and immune processes. The results herein may have implications for the development of fetal testing to assess placental function and fetal organ maturity. [ABSTRACT FROM AUTHOR]

Highlights • Male placentas and cord serum show an immunosuppressive immune signature. • Male neonates showed low umbilical serum TNF-α and high IL-10 levels and gene expression. • IL-1β expression was stimulated by VD metabolites in cultured trophoblasts. Abstract Clinical and epidemiological evidence supports that pregnancies carrying a male fetus are more vulnerable to infections and preterm birth, probably due to testosterone immunosuppressive properties. In human placentas, testosterone lowers the expression of CYP27B1 , the vitamin D (VD)-activating enzyme, diminishing cathelicidin synthesis, a potent VD-dependent antimicrobial peptide (AMP). VD also stimulates other AMPs, including defensins. To get insights into the increased male vulnerability mechanisms, we investigated the relationship between fetal sex and the immunoendocrine milieu at the fetoplacental unit. For this, umbilical vein serum and placental samples were collected from healthy newborns. In males' serum, testosterone levels were significantly higher and negatively associated with TNF-α, a cytokine that strengthens the immune response. Males showed lower serum TNF-α and increased levels and gene expression of the immunosuppressive cytokine IL-10. Only in female samples there was a positive association (P < 0.05) between AMPs and both TNF-α and CYP27B1 and between 25-hydroxyvitamin D 3 and IL-1β serum levels. Accordingly, VD-metabolites (25-hydroxyvitamin D 3 , calcitriol) significantly stimulated IL-1β gene expression in cultured trophoblasts. Interestingly, IL-1β mRNA correlated positively with defensins (P < 0.05) in males, but not with cathelicidin expression, which was significantly diminished in comparison to females. Our data suggest that high umbilical serum testosterone and IL-10 in males could explain reduced TNF-α levels and lack of association between VD-dependent innate immunity markers and proinflammatory cytokines expression in the fetoplacental unit. Altogether, our observations imply a restricted basal immune milieu in males compared to females, which may help understand the higher male susceptibility to adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is associated with excessive oxidative stress which may affect placental vascular function. Cholesterol homeostasis is crucial for maintaining fetoplacental endothelial function. We aimed to investigate whether and how GDM affects cholesterol metabolism in human fetoplacental endothelial cells (HPEC). HPEC were isolated from fetal term placental arterial vessels of GDM or control subjects. Cellular reactive oxygen species (ROS) were detected by H 2 DCFDA fluorescent dye. Oxysterols were quantified by gas chromatography–mass spectrometry analysis. Genes and proteins involved in cholesterol homeostasis were detected by real-time PCR and immunoblotting, respectively. Cholesterol efflux was determined from [ 3 H]-cholesterol labeled HPEC and [ 14 C]-acetate was used as cholesterol precursor to measure cholesterol biosynthesis and esterification. We detected enhanced formation of ROS and of specific, ROS-derived oxysterols in HPEC isolated from GDM versus control pregnancies. ROS-generated oxysterols were simultaneously elevated in cord blood of GDM neonates. Liver-X receptor activation in control HPEC by synthetic agonist TO901319, 7-ketocholesterol, or 7β-hydroxycholesterol upregulated ATP-binding cassette transporters (ABC)A1 and ABCG1 expression, accompanied by increased cellular cholesterol efflux. Upregulation of ABCA1 and ABCG1 and increased cholesterol release to apoA-I and HDL 3 (78 ± 17%, 40 ± 9%, respectively) were also observed in GDM versus control HPEC. The LXR antagonist GGPP reversed ABCA1 and ABCG1 upregulation and reduced the increased cholesterol efflux in GDM HPEC. Similar total cellular cholesterol levels were detected in control and GDM HPEC, while GDM enhanced cholesterol biosynthesis along with upregulated 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and sterol O-acyltransferase 1 (SOAT1) mRNA and protein levels. Our results suggest that in GDM cellular cholesterol homeostasis in the fetoplacental endothelium is modulated via LXR activation and helps to maintain its proper functionality. [ABSTRACT FROM AUTHOR]

Background: We studied associations of number of daily cigarettes in the first trimester with placental weight and birthweight in women who smoked throughout pregnancy, and in women who stopped smoking after the first trimester.Methods: We included all women with delivery of a singleton in Norway (n = 698 891) during 1999-2014, by using data from the Medical Birth Registry of Norway. We assessed dose-response associations by applying linear regression with restricted cubic splines.Results: In total, 12.6% smoked daily in the first trimester, and 3.7% stopped daily smoking. In women who smoked throughout pregnancy, placental weight and birthweight decreased by number of cigarettes; however, above 11-12 cigarettes we estimated no further decrease (Pnon-linearity < 0.001). Maximum decrease in placental weight in smokers compared with non-smokers was 18.2 g [95% confidence interval (CI): 16.6 to 19.7], and for birthweight the maximum decrease was 261.9 g (95% CI: 256.1 to 267.7). In women who stopped smoking, placental weight was higher than in non-smokers and increased by number of cigarettes to a maximum of 16.2 g (95% CI: 9.9 to 22.6). Birthweight was similar in women who stopped smoking and non-smokers, and we found no change by number of cigarettes (Pnon-linearity < 0.001).Conclusions: In women who smoked throughout pregnancy, placental weight and birthweight decreased non-linearly by number of cigarettes in the first trimester. In women who stopped smoking, placental weight was higher than in non-smokers and increased linearly by number of cigarettes; birthweight was almost similar to that of non-smokers. [ABSTRACT FROM AUTHOR]

Background Half-Fourier acquisition single-shot turbo spin-echo (HASTE) imaging is now widely used for placental and fetal imaging because of its rapidity and low sensitivity to fetal movement. If placental dysfunction is also predicted by quantitative value obtained from HASTE image, then it might be beneficial for evaluating placental wellbeing. Purpose To ascertain the most suitable magnetic resonance (MR) signal indexes reflecting placental function using HASTE imaging. Material and Methods This retrospective study included 37 consequent patients who had given informed consent to MR imaging (MRI) examinations. All had undergone MRI examinations between February 2014 and June 2015. First, the correlation between T2-relaxation time of normal placenta and gestational age (GA) was examined. Second, correlation between signal intensity ratios (SIRs) using HASTE imaging and placental T2-relaxation time were assessed. The SIRs were calculated using placental signal intensity (SI) relative to the SI of the amniotic fluid, fetal ocular globes, gastric fluid, bladder, maternal psoas major muscles, and abdominal subcutaneous adipose tissue. Results Among the 37 patients, the correlation between T2-relaxation time of the 25 normal placentas and GA showed a moderately strong correlation (Spearman rho = -0.447, P = 0.0250). The most significant correlation with placental T2-relaxation time was observed with the placental SIR relative to the maternal psoas major muscles (SIRpl./psoas muscle) (Spearman rho = -0.531, P = 0.0007). Conclusion This study revealed that SIRpl./psoas muscle showed the best correlation to placental T2-relaxation time. Results show that SIRpl./psoas muscle might be optimal as a clinically available quantitative index of placental function. [ABSTRACT FROM AUTHOR]

Introduction: Current knowledge of the fetoplacental vasculature in fetal growth restriction (FGR) due to placental dysfunction focuses on the microvasculature rather than the macrovasculature. The aim of this study was to investigate the feasibility of computed tomography angiography to analyze the fetoplacental macrovasculature in normal and FGR pregnancies.Material and Methods: We included 29 placentas (22-42 weeks of gestation) from normal birthweight pregnancies and eight placentas (26-37 weeks of gestation) from FGR pregnancies (birthweight < -15% and abnormal umbilical Doppler flow). We performed postpartum placental computed tomography angiography followed by semi-automatic three-dimensional image segmentation.Results: A median of nine (range seven to eleven) vessel generations was identified. In normal birthweight placentas, gestational age was positively linearly correlated with macrovascular volume (p = 0.002), vascular surface area (p < 0.0005) and number of vessel junctions (p = 0.012), but not with vessel diameter and inter-branch length. The FGR placentas had a lower weight (p = 0.004) and smaller convex volume (p = 0.022) (smallest convex volume containing the macrovasculature); however, macrovascular volume was not significantly reduced. Hence, macrovascular density given as macrovascular outcomes per placental volume was increased in FGR placentas: macrovascular volume per convex volume (p = 0.004), vascular surface area per convex volume (p = 0.004) and number of vessel junctions per convex volume (p = 0.037).Conclusions: Evaluation of the fetoplacental macrovasculature is feasible with computed tomography angiography. In normal birthweight placentas, macrovascular volume and surface area increase as pregnancy advances by vessel branching rather than increased vessel diameter and elongation. The FGR placenta was smaller; however, the macrovascular volume was within normal range because of an increased macrovascular density. [ABSTRACT FROM AUTHOR]

Abnormal placental function is well-established as a major cause for poor pregnancy outcome. Placental blood flow within the maternal uteroplacental compartment, the fetoplacental circulation or both is a vital factor in mediating placental function. Impairment in flow in either or both vasculatures is a significant risk factor for adverse pregnancy outcome, potentially impacting maternal well-being, affecting immediate neonatal health and even influencing the long-term health of the infant. Much remains unknown regarding the mechanistic underpinnings of proper placental blood flow. This review highlights the currently recognized molecular and cellular mechanisms in the development of normal uteroplacental and fetoplacental blood flows. Utilizing the entities of preeclampsia and fetal growth restriction as clinical phenotypes that are often evident downstream of abnormal placental blood flow, mechanisms underlying impaired uteroplacental and fetoplacental blood flows are also discussed. Deficiencies in knowledge, which limit the efficacy of clinical care, are also highlighted, underscoring the need for continued research on normal and abnormal placental blood flows. [ABSTRACT FROM AUTHOR]

Maternal malnutrition during pregnancy impacts fetal growth, with developmental consequences that extend to later life outcomes. In underdeveloped countries, this malnutrition typically takes the form of poor dietary protein content and quality, even if adequate calories are consumed. Here, we report the establishment of a nonhuman primate model of gestational protein restriction (PR) in order to understand how placental function and pregnancy outcomes are affected by protein deficiency. Rhesus macaques were assigned to either a control diet containing 26% protein or switched to a 13% PR diet prior to conception and maintained on this PR diet throughout pregnancy. Standard fetal biometry, Doppler ultrasound of uteroplacental blood flow, ultrasound-guided amniocentesis, and contrast-enhanced ultrasound (CE-US) to assess placental perfusion were performed mid-gestation (gestational day 85 [G85] where term is G168) and in the early third trimester (G135). Our data demonstrate that a 50% reduction in dietary protein throughout gestation results in reduced placental perfusion, fetal growth restriction, and a 50% rate of pregnancy loss. In addition, we demonstrate reduced total protein content and evidence of fetal hypoxia in the amniotic fluid. This report highlights the use of CE-US for in vivo assessment of placental vascular function. The ability to detect placental dysfunction, and thus a compromised pregnancy, early in gestation, may facilitate the development of interventional strategies to optimize clinical care and improve long-term offspring outcomes, which are future areas of study in this new model. [ABSTRACT FROM AUTHOR]

Objective Women with repaired coarctation of the aorta (rCoA) are at risk of hypertensive disorders and other complications during pregnancy. Hypertensive disorders in pregnant women are associated with inadequate uteroplacental flow, which is related to adverse offspring outcome. The aim of this study was to investigate the relationship of maternal cardiac function, placental function and pregnancy complications in women with rCoA. Methods We included 49 pregnant women with rCoA and 69 controls from the prospective ZAHARA-studies (Zwangerschap bij Aangeboren HARtAfwijkingen, pregnancy in congenital heart disease). Clinical evaluation, echocardiography and uteroplacental Doppler flow (UDF) measurements were performed at 20 and 32 weeks gestation. Univariable regression analysis was performed. Results Comparison of rCoA and healthy women. In women with rCoA, tricuspid annular plane systolic excursion (TAPSE) decreased during pregnancy (25.7 mm to 22.8 mm, P = 0.006). UDF indices and pregnancy complication rates were similar in both groups. Offspring of rCoA women had lower birth weight (3233 g versus 3578 g, P = 0.001), which was associated with β-blocker use during pregnancy (β = − 418.0, P = 0.01). Association of cardiac function and UDF. Right ventricular (RV) function before pregnancy (TAPSE) and at 20 weeks gestation (TAPSE and RV fractional area change) were associated with impaired UDF indices (umbilical artery pulsatility index at 20 weeks β = − 0.02, P = 0.01, resistance index at 20 and 32 weeks β = − 0.01, P = 0.02 and β = − 0.02, P = 0.01 and uterine artery pulsatility and resistance index at 20 weeks gestation β = − 0.02, P = 0.05 and β = − 0.01, P = 0.02). Conclusions Women with rCoA tolerate pregnancy well. However, RV function is altered and is associated with impaired placentation. [ABSTRACT FROM AUTHOR]

Objectives: Mitochondrial oxidative phosphorylation is the key energy source for placental functions and fetal growth. The purpose of this study was to investigate the function of placenta in high risk pregnancies by measuring mitochondrial respiratory chain complex (RCC) activities, and to evaluate the correlation between double test risk ratio and RCC activities.Methods: The placenta samples were collected from 50 pregnant women. The controls consisted of 20 normal uncomplicated pregnancies and the study group (n = 30) consisted of preeclampsia (PE), intrauterin growth restriction (IUGR), advanced maternal age (AMA), twins and preterm deliveries. Complexes I, II-III, IV and citrate synthase (CS) activities were measured by spectrophotometric assays.Results: Complexes I, II-III and IV activities were significantly lower in the study group than the controls (p < 0.05). Complexes I and II-III activities were significantly reduced in placenta of preterm deliveries compared with the controls (p < 0.003). Double test risk ratio was above the cut-off limit (1:300) in 43% of the study group in which decreased complexes I and II-III activities were observed.Conclusions: Impaired placental mitochondria RCC functions can lead to adverse pregnancy outcomes. Pregnant women with high risk in double test should be monitored carefully in terms of PE, IUGR and preterm delivery. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is an important cause of maternal and fetal morbidity and mortality that is associated with decreased placental perfusion. In the present study, vascular corrosion casting was used to investigate the differences in structural changes of the fetoplacental vasculature between normal and pre-eclamptic placentas. An improved epoxy resin vascular casting technique was used in the present study. Casting media were infused into 40 normal and 40 pre-eclamptic placentas through umbilical arteries and veins in order to construct three dimensional fetoplacental vasculatures. The number of branches, diameter, morphology and peripheral artery-to-vein ratio were measured for each specimen. The results indicated that the venous system of normal placentas was divided into 5-7 grades of branches and the volume of the vascular bed was 155.5±45.3 ml. In severe pre-eclamptic placentas, the volume was 106.4±36.1 ml, which was significantly lower compared with normal placentas (P<0.01). The venous system of pre-eclamptic placentas was divided into 4-5 grades of branches, which was much more sparse compared with normal placentas. In additions, the diameters of grade 1-3 veins and grade 2-3 arteries were significantly smaller in severe pre-eclampsia (P<0.05). In conclusion, pre-eclamptic placentas displayed a decreased volume of vascular bed, smaller diameters of grade 1-3 veins and grade 2-3 arteries, and an increased peripheral artery-to-vein ratio, which may be a cause of the placental dysfunction during severe pre-eclampsia. [ABSTRACT FROM AUTHOR]

The placenta is the link between mother and fetus and its function is central to a successful pregnancy. The predominant theory within the literature is that the development of placental dysfunction is a result of abnormal trophoblast invasion early in pregnancy. Knowledge of the development of the early placenta and the establishment of the fetomaternal circulation assists in understanding the origins of placental dysfunction which manifest later in pregnancy. Perinatally, chronic placental dysfunction may result in a growth-restricted fetus, maternal problems such as gestational hypertension, pre-eclampsia, eclampsia and pregnancy complications such as placental abruption, preterm labour and delivery. In addition, the growth-restricted fetus and the mother are at an increased risk of a myriad of disorders later in life. The role of ultrasound in the assessment of first trimester pregnancy is evolving with the potential for value in the prediction of placental function in later pregnancy. This review will address two aims, first to describe the development of the placenta from fertilisation to 12 weeks' gestation, correlating this with first trimester ultrasound findings. Second, to describe the link between placental development and function later in pregnancy. Understanding the link between early placental development and later placental function is essential in directing the focus of new research addressing the role of ultrasound in the first trimester in the prediction of adverse obstetric outcomes. [ABSTRACT FROM AUTHOR]

Background: Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes. Methods: This is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIVuninfected pregnant women were enrolled at 12-20 weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants. Results: The 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0-1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (≥ 2 episodes of symptomatic malaria or ≥ 50% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80-111.6) and 4.06 (1.73-9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRR = 3.27 (1.32-8.12) and aRR = 7.07 (2.84-17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46-21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy. Conclusion: Higher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes. [ABSTRACT FROM AUTHOR]

Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis, it is unknown whether it facilitates the gestational adaptations in lipid metabolism. To address this question, biochemical profiling, protein quantification, and gene expression studies were used, and gestational metabolic changes in T0901317-treated wild-type mice and Lxrab-/- mutants were investigated. Here, we show that altered LXR signaling contributes to the enhanced lipogenesis in early pregnancy by increasing the expression of hepatic Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of LXR with T0901317 and the genetic ablation of its two isoforms disrupted the increase in hepatic fatty acid biosynthesis and the development of hypertriglyceridemia during early gestation. We also demonstrate that absence of LXR enhances maternal white adipose tissue lipolysis, causing abnormal accumulation of triglycerides, cholesterol, and free fatty acids in the fetal liver. Together, these data identify LXR as an important factor in early-pregnancy lipogenesis that is also necessary to protect against abnormalities in fetoplacental lipid homeostasis. [ABSTRACT FROM AUTHOR]

Because reproduction is essential for all life, it is central to our understanding of all aspects of biology. The Society for Reproductive Biology (SRB) 2016 conference held on the Gold Coast (Qld, Australia) displayed the current breadth of reproductive research in Australia and New Zealand, with additional insights from world leaders in the field. This conference review provides a focused summary of the key questions, emerging ideas and novel technologies that were presented in the symposia. Presented research demonstrated key advances in how stem cell biology may allow us to better understand pluripotency, as well as how environmental and lifestyle factors, such as circadian disruption, smoking, alcohol and diet, affect gametogenesis, embryo implantation, placental function and reproductive capacity. Sessions also highlighted the role of reproductive biology in providing insight into the mechanisms and processes governing a wide range of biological science disciplines, including cancer research and therapies, oncofertility, conservation of native species and chronic non-communicable diseases. Recurring themes included the importance of male and female gamete quality for reproductive potential and the critical and varied roles of the placenta in the maintenance of a healthy pregnancy. Dysregulation of reproductive processes can contribute to a variety of pathological states that affect future health, fertility and fecundity. Research being conducted by the SRB has the potential to shape not only the fertility of the current generation, but also the health and reproductive viability of future generations. [ABSTRACT FROM AUTHOR]

Introduction: A vasa previa (VP) refers to aberrant chorionic vessels which can either connect the chorionic plate to a velamentous cord (type I) or a succenturiate or accessory lobe to the main placental mass (type II).Methods: We performed retrospective cohort study of 32 singleton pregnancies diagnosed with VP. The levels of maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) were measured at 15-18 weeks as part of the triple test screening for Trisomy 21. The data were subdivided according to the type of VP and compared with those of a control group with central cord insertion and no succenturiate or accessory placental lobe.Results: Twenty one (65.6%) parturient women presented with VP type I and 11 (34.4%) with VP type II. The mean birthweight and placental weight was significantly higher in pregnancies with VP type II than in pregnancies with VP with VP type I (3037.3±400.9 gr vs 2493.5±491.6 gr; p=0.004 and 511.0±47.2 gr vs 367.1±64.3 gr; p<0.0001; respectively). The mean hCG level in VP type II was significantly (p<0.001) higher than those with type I (2.38MoM vs 1.17MoM) and compared to controls (2.38MoM vs 0.99MoM).Conclusions: There is no obvious impact on both placental and fetal growth in VP type II. By contrast, VP type I is associated with slower feto-placental growth secondary to impaired development and biological functions of the placenta during the first half of pregnancy. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 30-year-old nulliparous woman who has opted for preimplantation genetic diagnosis (PGD) as she was a carrier of Robertsonian translocation. Topics discussed include performing non-invasive cell-free DNA (cfDNA) testing, identifying confined placental mosaicism (CPM) and diagnosing uniparental disomy (UPD).

Background Gestational diabetes mellitus (GDM) is a pathological state of glucose intolerance associated with adverse pregnancy outcomes and an increased risk of developing maternal type 2 diabetes later in life. The mechanisms underlying GDM development are not fully understood. We examined the pathophysiology of GDM through comprehensive metabolic profiling of maternal urine, using participants from a longitudinal cohort of normal pregnancies and pregnancies complicated by GDM. Methods Based on ultra-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry, an untargeted metabolomics study was performed to explore the differences in the urinary metabolome of GDM cases and healthy controls over the course of pregnancy. Multilevel statistical approaches were employed to address the complex metabolomic data obtained from a longitudinal cohort. Results The results indicated that tryptophan and purine metabolism was associated with GDM. The tryptophan-kynurenine pathway was activated in the GDM subjects before placental hormones or the fetoplacental unit could have produced any physiological effect. Hypoxanthine, xanthine, xanthosine, and 1-methylhypoxanthine were all elevated in the urine metabolome of subjects with GDM. Catabolism of purine nucleosides leads ultimately to the production of uric acid, which discriminated the subjects with GDM from controls. Conclusions The results support the notion that GDM may be a predisposed condition, or prediabetic state, which is manifested during pregnancy. This challenges the conventional view of the pathogenesis of GDM, which assumes placental hormones are the major causes of insulin resistance in GDM. [ABSTRACT FROM AUTHOR]

Background. Doppler velocimetry (DV) is widely used to assess the vascular formation of the placenta in fetal growth restriction (FGR) and to estimate the haemodynamic condition of the growth-restricted fetus. Umbilical artery (UA) flow is essentially placental, rather than fetal. Hence, DV provides information about the fetal side of the placenta and, alongside placental histopathology, it could possibly help to decipher aetiopathogenesis in FGR cases. Objective. To correlate UA DV findings occurring in FGR with placental findings. Methods. The study was prospective and conducted in a low-income setting. A total of 130 non-anomalous singleton FGR pregnancies (≥24 weeks) were included in the study. All pregnancies were confirmed to be small for gestational age (SGA) after the birth of the neonate. The placental lesions and neonatal outcomes were correlated with DV findings before delivery: 65 cases with normal DV results constituted group 1, and group 2 had 65 cases with abnormal DV results such as reduced flow, absent UA end diastolic flow or reversal of UA end diastolic flow. Results. Group 2 had significantly lower mean (standard deviation) birth weights of 1.59 (0.4) kg v. 1.87 (0.23) kg for group 1 (p<0.001). Considerably higher NICU mortality was seen in group 2 (30.5%) compared with group 1 (6.7%) (p<0.001). The group 2 placentas weighed less, had a higher number of maternal underperfusion (MUP) lesions, higher levels of calcification. Among lesions of MUP, 4 lesions i.e. villous infarction (p<0.001), villous agglutination (p<0.001), syncytial knots (p=0.003) and intervillous fibrin deposition (p=0.001) were present in significantly higher numbers in the abnormal Doppler group compared with the normal Doppler group. Abnormal Doppler had a sensitivity of 80% and specificity of 92.3% for abnormal placental pathology (placental lesions >3). Conclusions. There was a significantly higher number of MUP lesions and neonatal morbidity in SGA patients with abnormal DV findings. [ABSTRACT FROM AUTHOR]

Maternal vitamin D deficiency has been implicated in a range of pregnancy complications including preeclampsia, preterm birth and intrauterine growth restriction. Some of these adverse outcomes arise from alterations in placental function. Indeed, vitamin D appears critical for implantation, inflammation, immune function and angiogenesis in the placenta. Despite these associations, absence of the placental vitamin D receptor in mice provokes little effect. Thus, interactions between maternal and fetal compartments are likely crucial for instigating adverse placental changes. Indeed, maternal vitamin D deficiency elicits changes in glucocorticoid-related parameters in pregnancy, which increase placental and fetal glucocorticoid exposure. As in utero glucocorticoid excess has a well-established role in eliciting placental dysfunction and fetal growth restriction, this review proposes that glucocorticoids are an important consideration when understanding the impact of vitamin D deficiency on placental function and fetal development. [ABSTRACT FROM AUTHOR]

Objectives: To clarify whether ultrasonographic evaluations of fetoplacental underperfusion using umbilical artery (UmA) Doppler indices at 36 weeks’ gestation can predict maternal hypertension at later gestation. Methods: Normotensive pregnant women who underwent an ultrasound scan at 36 weeks’ gestation and delivered singleton infants at term between 2012 and 2013 were prospectively enrolled. UmA Doppler and maternal blood pressure results at 36 weeks’ gestation in cases with pregnancy-induced hypertension (PIH) at later gestation were compared with a control group. Results: Thirty-nine and 775 cases were classified into the PIH and control group, respectively. The UmA pulsatility index (PI) and maternal systolic blood pressure (SBP) at 36 weeks’ gestation were higher in the PIH group than in control group (UmA-PI: 0.88 vs. 0.80,p = 0.002; SBP: 126 mmHg vs. 112 mmHg,p < 0.001). The area under the ROC curve for the prediction of PIH by combining the UmA-PI and SBP was 0.867 (95% confidence interval (CI): 0.781, 0.954). The detection rate for PIH was 64.0% with a 10% false-positive rate. Conclusions: An increased UmA-PI at 36 weeks’ gestation is associated with the occurrence of PIH at later gestation. This result may indicate the possibility to detect fetoplacental underperfusion ultrasonically. [ABSTRACT FROM AUTHOR]

Here we describe clinicopathologic features of Ebola virus disease in pregnancy. One woman infected with Sudan virus in Gulu, Uganda, in 2000 had a stillbirth and survived, and another woman infected with Bundibugyo virus had a live birth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malarial parasite pigment-laden macrophages. These data suggest that trophoblast infection may be a mechanism of transplacental ebolavirus transmission. [ABSTRACT FROM AUTHOR]

The human placenta fulfills a variety of essential functions during prenatal life. Several ABC transporters are expressed in the human placenta, where they play a role in the transport of endogenous compounds and may protect the fetus from exogenous compounds such as therapeutic agents, drugs of abuse, and other xenobiotics. To date, considerable progress has been made toward understanding ABC transporters in the placenta. Recent studies on the expression and functional activities are discussed. This review discusses the placental expression and functional roles of several members of ABC transporter subfamilies B, C, and G including MDR1/P-glycoprotein, the MRPs, and BCRP, respectively. Since placental ABC transporters modulate fetal exposure to various compounds, an understanding of their functional and regulatory mechanisms will lead to more optimal medication use when necessary in pregnancy. [ABSTRACT FROM AUTHOR]

Prenatal exposure to excessive glucocorticoids (GCs) leads to intrauterine growth retardation and fetal programming of adult health and disease through deregulation of placental functions. Placental secretion of insulin-like growth factor-I (IGF-I) plays a critical role in the regulation of placental development and function. However, it remains elusive whether GCs affect placental functions through glucocorticoid receptor (GR)-mediated transcriptional regulation of IGF-I gene. In this study, human placental choriocarcinoma (BeWo) cells before and after syncytialization were used as cytotrophoblast and syncytiotrophoblast models, respectively, to explore the effects of dexamethasone (Dex) on transcriptional regulation of IGF-I gene at both stages. Dex significantly inhibited ( P < 0.05) cell proliferation in cytotrophoblasts and down-regulated amino acid transporter SLC7A5 in syncytiotrophoblasts. Concurrently, the abundance of IGF-I mRNA and its transcript variants, together with IGF-I level in culture media, were significantly reduced, in association with significantly enhanced ( P < 0.05) GR phosphorylation. GR antagonist RU486 was able to abolish all these effects. Two glucocorticoid response elements (GREs) were predicted in the promoter regions of IGF-I gene. GR binding to GRE1 was significantly enriched ( P < 0.05) in both cytotrophoblasts and syncytiotrophoblasts, but that to GRE2 was significantly diminished ( P < 0.05) in cytotrophoblasts but not in syncytiotrophoblasts, in response to Dex treatment. IGF-I supplementation completely rescued Dex-induced cell cycle arrest but not SLC7A5 down-regulation, indicating different regulatory mechanisms. Taken together, our results suggest that GR-mediated transcriptional regulation of IGF-I is involved in Dex-induced inhibition of placental cell proliferation and function. [ABSTRACT FROM AUTHOR]

Eicosanoids are signaling lipids known to regulate several physiological processes in the mammalian placenta, including the initiation of parturition. Though all amniotes construct similar extraembryonic membranes during development, the composition and function of eicosanoids in extraembryonic membranes of oviparous reptiles is largely unknown. The majority of effort placed in eicosanoid investigations is typically targeted toward defining the role of specific compounds in disease etiology; however, comprehensive characterization of several pathways in eicosanoid synthesis during development is also needed to better understand the complex role of these lipids in comparative species. To this end, we have examined the chorioallantoic membrane (CAM) of the American alligator ( Alligator mississippiensis ) and domestic chicken ( Gallus gallus ) during development. Previously, our lab has demonstrated that the CAM of several oviparous species shared conserved steroidogenic activity, a feature originally attributed to mammalian amniotes. To further explore this, we have developed a liquid chromatography/tandem mass spectrometry method that is used here to quantify multiple eicosanoids in the CAM of two oviparous species at different stages of development. We identified 18 eicosanoids in the alligator CAM; the cyclooxygenase (COX) pathway showed the largest increase from early development to later development in the alligator CAM. Similarly, the chicken CAM had an increase in COX products and COX activity, which supports the LC-MS/MS analyses. Jointly, our findings indicate that the CAM tissue of an oviparous species is capable of eicosanoid synthesis, which expands our knowledge of placental evolution and introduces the possibility of future comparative models of placental function. [ABSTRACT FROM AUTHOR]

Background: Angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) are known to be involved in fetoplacental angiogenesis adequacy, which is a primary determinant of fetal growth. Regional variations in Ang1, Ang2, and Tie2 remain unknown, although fetoplacental vascularity and gene expressions differ between the placental center and the periphery.Objective: The aim of this study was to test the hypothesis that there are regional variations in the expression of these angiopoietins in human placentas from uncomplicated term and near term pregnancies.Study Design: In this prospective study, central and peripheral samples were collected from fresh placentas from normal-term and near-term pregnancies delivered by Cesarean section (n = 7, 36-41 week gestation) prior to the onset of labor. Regional differences in Ang1, Ang2, and Tie2 protein expressions were measured by Western blot and densitometric analyses with b-actin normalization, and their fetoplacental regional localization assessed by immunohistochemistry. The Ang1 and Ang2 ratios at central and peripheral sites were determined. Statistical analysis was performed using Student's t-test.Results: Ang1 protein expression was higher in the placental periphery than in the center (2.48 ± 0.42 versus 1.74 ± 0.27, p = 0.01). In contrast, Ang2 protein expression was greater in the placental center than in the periphery (10.10 ± 1.82 versus 7.15 ± 1.12, respectively, p = 0.03). The Ang1-Ang2 ratio reflected these differential expressions. Tie2 protein expression was higher in the placental periphery than in the center (0.21 ± 0.02 versus 0.16 ± 0.02, p = 0.003). The immunoreactivity of Ang1 and Tie2 was stronger in the periphery than in the center, and that of Ang2 was stronger in the center than in the periphery.Conclusions: Ang1, Ang2, and Tie2 are differentially expressed in placental center and periphery. Ang1/Ang2 ratio reflects this regional variation in the angiogenic balance that has implications for fetoplacental villous angiogenesis. The results also demonstrate the importance of considering the location of placental sampling sites for any future investigations of fetoplacental villous angiogenesis. [ABSTRACT FROM AUTHOR]

The prevalence of placental malaria and its impact on maternal and newborn outcomes have been poorly documented in periurban settings of Burkina Faso. Peripheral and placental blood from 320 mothers, and cord blood from their newborns were collected through a cross-sectional study and used to prepare thick and thin blood films. Maternal haemoglobin concentration and birthweight were also measured. The overall malaria parasitaemia prevalence in peripheral, placental and cord blood was of 17·2, 9·1 and 0·9%, respectively. Plasmodium falciparum was the sole species found in all cases and the mean parasite density in placental blood was 4·5 ± 0·8 parasites µL-1. Primigravida (aOR: 3·5; 95% CI (1·1-11·2)) and women who did not use a bed net (aOR: 2·6; 95% CI (1·1-6·3)), were at higher odds of placental malaria infection. Women with placental parasitaemia were at increased odds of maternal anaemia (aOR: 3·1; 95% CI (1·3-7·4)). There was no odds difference for LBW between mothers with placental parasitaemia and those without. Placental malaria parasitaemia resulted in a significant mean birthweight reduction of 200 g. Placental malaria infection is higher in primigravida. Use of insecticide-treated bed nets should be therefore emphasized for primigravida during the first antenatal care visit. [ABSTRACT FROM AUTHOR]

Problem The chronic placental insufficiency is the most common cause of intrauterine hypoxia, retardation of fetal growth, and other threatening conditions. Immune disturbances may occur in the system 'mother-placenta-fetus.' Method of study Biochemical blood indicators were studied on an automated biochemical analyzer. Pattern of lymphocyte subpopulations was detected by direct membrane immunofluorescence. Results Study revealed imbalance of immune parameters, caused by placental insufficiency (increase natural killers ( CD16+, CD56+), B lymphocytes ( CD19+ CD3−), T and B lymphocytes with HLA- DR+ antigen, and early activation of immune cells (by CD25+), as well as disorders in apoptotic mechanisms (by CD95+)). Conclusion Placental insufficiency leads to abnormalities of the immune system in pregnant, parturient women and maternity patients which were evaluated by localization of activation markers CD25+ CD95+ on the CD3+, CD4+, CD8+, CD16+, CD56+ lymphocytes. This is reflected in the change of lymphocyte functions in newborns. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to correlate between pregnancy outcome and placental pathology in emergent cesarean deliveries (ECD) for non-reassuring-fetal-heart-rate (NRFHR) performed in women in their active phase of labor versus those performed in non-laboring women.Methods: A retrospective cohort study. Data were reviewed for all pregnancies necessitating ECD for NRFHR between January 2009 and December 2013. Maternal outcome, neonatal outcome, and placental pathology parameters were compared between ECDs performed during active phase of labor and those performed before the active phase of labor (non-labor group).Results: During the study period, a total of 661 ECDs were performed due to NRFHR. Compared with the active labor group (n = 335), the non-labor group (n = 326) had more pre-eclampsia (p = 0.033), small for gestational age (SGA) (p = 0.016), and preterm labor (p < 0.001). Worse composite neonatal outcome was observed in the non-labor group compared with the active labor group, p < 0.001. By a stepwise logistic regression model, non-labor was independently associated with adverse neonatal outcome (1.88 OR CI; 1.19-2.96, p = 0.007). Placental inflammatory lesions were more common in the active labor group (p= 0.043), and abnormal cord insertions were more common in the non-labor group (p = 0.002) as well as placental weight <10th% (p = 0.019).Conclusion: Higher rate of pregnancy complications, abnormal cord insertion, smaller placentas, and worse neonatal outcome are associated with ECD for NRFHR when performed before the phase of active labor. [ABSTRACT FROM AUTHOR]

Women with polycystic ovary syndrome (PCOS) have elevated circulating androgens during pregnancy and are at an increased risk of adverse pregnancy outcomes. Here we tested the hypotheses that maternal androgen excess decrease placental and fetal growth, and placental expression of markers of steroidogenesis, angiogenesis and sympathetic activity, and that acupuncture with low-frequency electrical stimulation prevents these changes. Pregnant rats were exposed to vehicle or testosterone on gestational day (GD)15-19. Low-frequency electroacupuncture (EA) or handling, as a control for the EA procedure, was given to control or testosterone exposed dams on GD16-20. On GD21, blood pressure was measured and maternal blood, fetuses and placentas collected. Placental steroid receptor expression and proteins involved in angiogenic, neurotrophic and adrenergic signaling were analyzed. EA did not affect any variables in control rats except maternal serum corticosterone, which was reduced. EA in testosterone exposed dams compared with controls increased systolic pressure by 30%, decreased circulating norepinephrine and corticosterone, fetal and placental weight and placental VEGFR1 and proNGF protein expression, and increased the VEGFA/VEGFR1 ratio, mature NGF (mNGF) and the mNGF/proNGF ratio. In conclusion, low-frequency EA in control animals did not have any negative influence on any of the studied variables. In contrast, EA in pregnant dams exposed to testosterone increased blood pressure and impaired placental growth and function, leading to decreased fetal growth. [ABSTRACT FROM AUTHOR]

Background: Surgical navigation technology directed at fetoscopic procedures is relatively underdeveloped compared with other forms of endoscopy. The narrow fetoscopic field of views and the vast vascular network on the placenta make examination and photocoagulation treatment of twin-to-twin transfusion syndrome challenging. Though ultrasonography is used for intraoperative guidance, its navigational ability is not fully exploited. This work aims to integrate 3D ultrasound imaging and endoscopic vision seamlessly for placental vasculature mapping through a self-contained framework without external navigational devices.Methods: This is achieved through development, integration, and experimentation of novel navigational modules. Firstly, a framework design that addresses the current limitations based on identified gaps is conceptualized. Secondly, integration of navigational modules including (1) ultrasound-based localization, (2) image alignment, and (3) vision-based tracking to update the scene texture map is implemented. This updated texture map is projected to an ultrasound-constructed 3D model for photorealistic texturing of the 3D scene creating a panoramic view of the moving fetoscope. In addition, a collaborative scheme for the integration of the modular workflow system is proposed to schedule updates in a systematic fashion. Finally, experiments are carried out to evaluate each modular variation and an integrated collaborative scheme of the framework.Results: The modules and the collaborative scheme are evaluated through a series of phantom experiments with controlled trajectories for repeatability. The collaborative framework demonstrated the best accuracy (5.2 % RMS error) compared with all the three single-module variations during the experiment. Validation on an ex vivo monkey placenta shows visual continuity of the freehand fetoscopic panorama.Conclusions: The proposed developed collaborative framework and the evaluation study of the framework variations provide analytical insights for effective integration of ultrasonography and endoscopy. This contributes to the development of navigation techniques in fetoscopic procedures and can potentially be extended to other applications in intraoperative imaging. [ABSTRACT FROM AUTHOR]

The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, “PlaNet”, will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To assess the umbilical cord centrality, placental morphometrics, and functional efficiency in preeclampsia.Methods: Placental morphometry of normotensive (n = 69) and preeclamptic (n = 69) patients was evaluated.Results: There was a significant reduction in mean placental surface area (p = 0.0001), length (p = 0.0001), thickness (p = 0.016), and volume (p = 0.0001) in the preeclamptic than in the normotensive groups. Umbilical cord insertion was predominantly eccentric with marginal in early (29%) and late-onset preeclampsia (16%). Placental and birth weight was lower (p = 0.0001) in preeclampsia than in the normotensive group. Placental efficiency was reduced in early-onset preeclampsia.Conclusion: This study demonstrates reduced placental morphometrics with impaired placental efficiency in preeclampsia. [ABSTRACT FROM AUTHOR]

Uteroplacental development is a crucial step facilitating conceptus growth. Normal placental development comprises extensive placental angiogenesis to support fetoplacental transport, meeting the metabolic demands of the fetus. Compromised pregnancies due to maternal stressors such as over or undernutrition, maternal age or parity, altered body mass index, or genetic background result in altered vascular development of the placenta. This negatively affects placental growth and placental function and ultimately results in poor pregnancy outcomes. Nonetheless, the placenta acts as a sensor to the maternal stressors and undergoes modifications, which some have termed placental programming, to ensure healthy development of the conceptus. Sex steroid hormones such as estradiol-17β and progesterone, chemokines such as chemokine ligand 12, and angiogenic/vasoactive factors such as vascular endothelial growth factors, placental growth factor, angiopoietins, and nitric oxide regulate uteroplacental development and hence are often used as therapeutic targets to rescue compromised pregnancies. Interestingly, the presence of sex steroid receptors has been identified in the fetal membranes (developing fetal placenta). Environmental steroid mimetics known as endocrine disrupting compounds disrupt conceptus development and lead to transgenerational impairments by epigenetic modification of placental gene expression, which is another area deserving intense research efforts. This review attempts to summarize current knowledge concerning intrinsic and extrinsic factors affecting selected reproductive functions with the emphasis on placental development. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to measure the elasticity of normal placentas using the Virtual Touch quantification (VTQ) technique. Methods: This study was approved by the Institutional Ethics Committee. Fifty randomly selected, healthy pregnant women in their second trimester and 50 randomly selected, healthy pregnant women in their third trimester with a single fetus were included, and their placentas underwent VTQ through shear wave velocity (SWV) measurements. The measurements were performed at different locations to sample different areas of the placenta. Measurements were performed 3-4 times in each location, the mean shear wave velocities were calculated without the highest and lowest values of measurements in each region, and the results were compared. Results: The SWV of the placenta was 0.983±0.260 m/sec, and the minimal and maximal speed was 0.63 m/sec and 1.84 m/sec, respectively. There was no significant difference between the second and third trimester of VTQ of the placenta in terms of SWV (0.978±0.255 m/sec vs. 0.987±0.266 m/sec, P=0.711). The maternal age between second and third trimester was 27.9±4.3 years and 29.2±4.4 years, respectively; there was no significant difference between them (P=0.159). Conclusion: The results of this study show that the SWV of normal placenta tissue is 0.983±0.260 m/sec, it has little variation between the second and third trimesters, and the VTQ technique may potentially play an additional role in placenta evaluation. [ABSTRACT FROM AUTHOR]

Carpel morphogenesis is crucial for seed development, and fruit size and quality, and carpel number is one measure of the level of plant evolution. A comparative study of morphogenesis and gene modulation was initiated to study the ontogeny of bi- and tricarpellate fruits. In our study, ‘Xiangfei’ grapevine (Vitis vinifera) was used as the plant material because of its high tricarpellate occurrence. Results showed that congenital fusion was the main pathway for tricarpellate ovary ontogeny. There were three ventral sutures on tricarpellate fruits in the period of flowering, and this feature was absent from bicarpellate fruits. From 20 to 40 days after flowering (DAF), the growth rate of tricarpellate fruits was greater than that of bicarpellate fruits. FourVvYABBYgenes were identified from the grapevine genome by BLAST searches using the sequence of tomatoSlFASCIATED(SlFASis a protein that negatively regulates locule number). Real-time PCR determined the transcript levels of theVvYABBYgenes in bicarpellate and tricarpellate ovaries. Only the transcript level ofVvYAB5in tricarpellate ovaries was lower than that in bicarpellate ovaries in different developmental periods.In situanalysis showed thatVvYAB5transcripts were detected in carpel primordia and placental tissue. Taken together, a tentative inference is that theVvYAB5gene might play a role in tricarpellate fruit formation. [ABSTRACT FROM PUBLISHER]

For clinical management of different forms of psychosis, both classical and atypical anti-psychotic drugs ( APDs) are available. These drugs are widely prescribed, even during pregnancy considering their minimal extra-pyramidal side effects and teratogenic potential compared to classical APDs. Among AAPDs, risperidone ( RIS) is a first-line drug of choice by physicians. The molecular weight of RIS is 410.49 g/mol; hence, it can easily cross the placental barrier and enter the foetal bloodstream. It is not known whether or not AAPDs like RIS may affect the developing placenta and foetus adversely. Reports on this issue are limited and sketchy. Therefore, this study has evaluated the effects of maternal exposure to equivalent therapeutic doses of RIS on placental growth, histopathological and cytoarchitectural changes, and to establish a relationship between placental dysfunction and foetal outcomes. Pregnant rats ( n = 24) were exposed to selected doses (0.8, 1.0 and 2.0 mg/kg) of RIS from gestation days 6-21. These dams were sacrificed; their placentas and foetuses were collected, morphometrically examined and further processed for histopathological examination. This study revealed that in utero exposure to equivalent therapeutic doses of RIS during organogenesis-induced placental dystrophy (size and weight), disturbed cytoarchitectural organization (thickness of different placental layers), histopathological lesions (necrosis in trophoblast with disruption of trophoblastic septa and rupturing of maternal-foetal interface) and intrauterine growth restriction of the foetuses. It may be concluded that multifactorial mechanisms might be involved in the dysregulation of structure and function of the placenta and of poor foetal growth and development. [ABSTRACT FROM AUTHOR]

Objectives: to propose the use of a Bayesian hierarchical model to study the allometric scaling of the fetoplacental weight ratio, including possible confounders. Methods: data from 26 singleton pregnancies with gestational age at birth between 37 and 42 weeks were analyzed. The placentas were collected immediately after delivery and stored under refrigeration until the time of analysis, which occurred within up to 12 hours. Maternal data were collected from medical records. A Bayesian hierarchical model was proposed and Markov chain Monte Carlo simulation methods were used to obtain samples from distribution a posteriori. Results: the model developed showed a reasonable fit, even allowing for the incorporation of variables and a priori information on the parameters used. Conclusions: new variables can be added to the modelfrom the available code, allowing many possibilities for data analysis and indicating the potential for use in research on the subject. [ABSTRACT FROM AUTHOR]

We investigated morphological differences in uterine epithelia of the reproductive cycle between two closely related viviparous skinks, Niveoscincus metallicus (lecithotrophic) and Niveoscincus ocellatus (placentotrophic), which have similar placental complexity but different degrees of placentotrophy. Scanning ( SEM) and transmission electron microscopy ( TEM) revealed that the uterine surface of non-reproductive females of both species is mainly covered by ciliated cells. As vitellogenesis begins, the uterine epithelium consists of ciliated and non-ciliated cells under a thin glycocalyx. Microvilli are greatly reduced at mid-pregnancy, and the uterus differentiates into two structurally distinct regions: the chorioallantoic and the omphaloplacenta. At late stages of pregnancy, the uterine epithelium of chorioallantoic placenta in both species is further ridged, forming a knobbly uterine surface. The ultrastructural evidence between N. metallicus and N. ocellatus cannot strictly account for the distinct differences in their placentotrophy; as yet unexplored molecular nutrient transport mechanisms that are not reflected in uterine ultrastructure must play significant roles in nutrient transportation. Characteristics consistent with a plasma membrane transformation were confirmed in both species. [ABSTRACT FROM AUTHOR]

Key points A correlation was found between in vivo umbilical artery Doppler velocimetry and resistance to fetal-side flow in the human ex vivo dually perfused placenta, highlighting that the fetoplacental vascular bed is a key site of resistance to umbilico-placental flow in pregnancy., We discovered high resistance and poor flow-mediated vasodilatory responses in placentas from pregnancies associated with fetal growth restriction (FGR)., Endothelial cells isolated from the FGR placentas and grown in static and flow culture showed a dysregulated phenotype, with biochemical signalling demonstrating a failed compensatory response to high blood-flow resistance., Abstract Increased vascular resistance and reduced fetoplacental blood flow are putative aetiologies in the pathogenesis of fetal growth restriction (FGR); however, the regulating sites and mechanisms remain unclear. We hypothesised that placental vessels dictate fetoplacental resistance and in FGR exhibit endothelial dysfunction and reduced flow-mediated vasodilatation (FMVD). Resistance was measured in normal pregnancies ( n = 10) and FGR ( n = 10) both in vivo by umbilical artery Doppler velocimetry and ex vivo by dual placental perfusion. Ex vivo FMVD is the reduction in fetal-side inflow hydrostatic pressure (FIHP) following increased flow rate. Results demonstrated a significant correlation between vascular resistance measured in vivo and ex vivo in normal pregnancy, but not in FGR. In perfused FGR placentas, vascular resistance was significantly elevated compared to normal placentas (58 ± 7.7 mmHg and 36.8 ± 4.5 mmHg, respectively; 8 ml min−1; means ± SEM; P < 0.0001) and FMVD was severely reduced (3.9 ± 1.3% and 9.1 ± 1.2%, respectively). In normal pregnancies only, the highest level of ex vivo FMVD was associated with the lowest in vivo resistance. Inhibition of NO synthesis during perfusion (100 μ m l-NNA) moderately elevated FIHP in the normal group, but substantially in the FGR group. Human placenta artery endothelial cells from FGR groups exhibited increased shear stress-induced NO generation, iNOS expression and eNOS expression compared with normal groups. In conclusion, fetoplacental resistance is determined by placental vessels, and is increased in FGR. The latter also exhibit reduced FMVD, but with a partial compensatory increased NO generation capacity. The data support our hypothesis, which highlights the importance of FMVD regulation in normal and dysfunctional placentation. [ABSTRACT FROM AUTHOR]

We report a case of a twin-reversed arterial perfusion (TRAP) sequence complication in monochorionic triplets, in which both normal fetuses were directly connected to the umbilical cord of the acardiac fetus, thus both acting as a pump twin. Doppler ultrasound showed a significant waveform pattern with two superposed systolic waveforms in the same vessel. After birth, placental findings confirmed the existence of two direct pump twins. The Doppler pattern described here may be of help to distinguish the existence of two pump twins in a triplet monochorionic pregnancy with TRAP. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) has been associated with adverse fetal outcomes in some studies. Second trimester Down syndrome screening markers reflect fetal and fetoplacental wellbeing. We aimed to compare markers of fetal and feto-placental wellbeing in women with OSA and low risk controls. Methods: A retrospective case-control study of pregnant women with OSA and available second trimester markers was performed. Controls were screened for sleep disordered breathing (SDB) at the time of delivery using a questionnaire. Women at low risk for OSA were selected. Marker levels were adjusted for gestational age and race and reported as multiples of median and later adjusted for body mass index (BMI). Results: Twenty-four OSA cases and 166 controls were identified. Women with OSA had a higher mean BMI when compared to controls (37.1 ± 12.7 versus 24.1 ± 5.1, p = 0.03). Estriol (uE3) multiples of the median (MoM) levels were lower in women with OSA compared to controls, even after adjusting for BMI, 0.74 (interquartile range (IQR) 0.45) versus 1.06 (IQR 0.38), respectively, p = 0.026. Once adjusted for BMI, alpha feto-protein (AFP) MoM levels were no longer significantly different in women with OSA compared to controls. Conclusion: OSA is associated with reduced serum uE3 levels, independently of BMI, possibly indicating fetal distress. [ABSTRACT FROM AUTHOR]

Vascular endothelial cadherin and β-catenin play a key role in establishment and maintenance of the endothelial monolayer integrity, regulation of vascular barrier function, and initiation of angiogenesis. The cadherin-catenin complex has been shown to be reduced in type 1 diabetic placenta, but the exact relationship between histopathologic findings and clinical data is not known. Immunohistochemistry of placental tissue from type 1, type 2, and gestational diabetes showed that diabetes per se might be compatible with normal levels of vascular endothelial (VE)-cadherin and β-catenin in fetoplacental vessels as long as the patient has not been treated with insulin. Immunoreactivity of VE-cadherin did correlate poorly with maternal glycemic control, as was investigated in this study, by birth weight, body mass index, and hemoglobin A1c (HbA1c). There was no correlation found between the immunoreactivity of β-catenin and birth weight, body mass index, or HbA1c. However our data did show a strong correlation between immunoreactivity and whether or not the patient had been treated with insulin. Patients diagnosed with gestational diabetes who had not been treated with insulin had similar levels of VE-cadherin and β-catenin to the control group, thus indicating that diabetes per se must not necessarily lead to a reduction. Our study suggests that therapeutic intervention using insulin in pregnancies complicated by diabetes might have potentially harmful effects on placental morphology. Future studies should further investigate these findings. [ABSTRACT FROM AUTHOR]