Placental Blood Research Articles

Contribution of placental 11β-HSD2 to the pathogenesis of preeclampsia.

Preeclampsia, a major human pregnancy-specific disorder, leads to maternal and fetal morbidity and mortality. Here we reported that 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an enzyme that degrades active glucocorticoids, is one of the key factors that contributes to preeclampsia development. In the pregnant rat model, we firstly confirmed that administration of 11β-HSD2 inhibitor carbenoxolone (CBX) subcutaneously or by placenta-targeted delivery system could lead to a decrease in placental 11β-HSD2 expression and activity and an increase in corticosterone level in placenta and maternal circulation. Then, we showed that subcutaneous administration and placenta-targeted delivery of CBX resulted in the hallmark of preeclampsia-like features including hypertension, proteinuria, renal damages as well as elevated circulatory soluble fms-like tyrosine kinase 1 (sFlt1) and increased sFlt1/placental growth factor (PlGF) ratio in pregnant rats. These animals displayed decreased trophoblast invasion in uterus, impaired spiral artery remodeling, and reduced placental blood flow. Preeclampsia-like features could also be induced by administration of dexamethasone in pregnant rats. In the cultured human trophoblast models, we found that cortisol only inhibited migration and invasion of the extravillous trophoblasts with 11β-HSD2 knockdown, and promoted sFlt1 release in the cultured syncytiotrophoblasts with 11β-HSD2 knockdown. Furthermore, we elucidated that cortisol stimulated a disintegrin and metalloprotease (ADAM)17 expression in placentas, thereby promoting sFlt1 release in placenta. Collectively, our study provided the evidence that placental 11β-HSD2 dysfunction plays a key role in the development of preeclampsia and immediately identified innovative target to counteract preeclampsia.

Three-dimensional power Doppler ultrasonography indicates that increased placental blood perfusion during the third trimester is associated with the risk of macrosomia at birth.

To investigate the association between placental blood perfusion and the occurrence of macrosomia at birth. This was a prospective cohort study including women with singleton pregnancies that aimed to measure placental blood perfusion using three-dimensional (3D) power Doppler ultrasonography in the second and third trimester. We acquired three indices of placental blood flow, including vascularization index (VI), flow index (FI), vascularization flow index (VFI), along with routine two-dimensional (2D) biometric measurements, including abdominal circumference (AC) and estimated fetal weight (EFW). Pregnancy outcomes were divided into two groups: newborns with a normal birth weight and those with macrosomia. We then compared all of the recorded variables between these two groups. We also determined the predictive efficiency of each variable using receiver-operating characteristic (ROC) curves. The placental 3D power Doppler indices, including VI and FI, were significantly higher in the third trimester of pregnancies developing macrosomia, but not during the second trimester, as compared to those with a normal birth weight. ROC curves analysis for third-trimester VI and FI suggested a slight ability to predict macrosomia; this was also the case for AC and EFW. Interestingly, VI showed high sensitivity and low specificity, while FI showed low sensitivity and high specificity; this was also the case for AC and EFW. Three-dimensional power Doppler ultrasound indices were significantly higher during the third-trimester for pregnancies developing macrosomia. However, these indices had only moderate ability to predict macrosomia.

Identifying new potential genetic biomarkers for HELLP syndrome using massive parallel sequencing.

Preeclampsia (PE) is a frequently occurring multisystemic disease affecting ~5% of pregnancies. PE patients may develop HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet), a mother and foetus life-threatening condition. Research into HELLP's genetic origin has been relatively unsuccessful, mainly because normal placental function and blood pressure regulation involve the fine-regulation of hundreds of genes. To identify new genes and mutations constituting potential biomarkers for HELLP syndrome. The present case-control study involved whole-exome sequencing of 79 unrelated HELLP women. Candidate variants were screened in a control population constituted by 176 individuals. Stringent bioinformatics filters were used for selecting potentially etiological sequence variants in a subset of 487 genes. We used robust in silico mutation modelling for predicting the potential effect on protein structure. We identified numerous sequence variants in genes related to angiogenesis/coagulation/blood pressure regulation, cell differentiation/communication/adhesion, cell cycle and transcriptional gene regulation, extracellular matrix biology, lipid metabolism and immunological response. Five sequence variants generated premature stop codons in genes playing an essential role in placental physiology (STOX1, PDGFD, IGF2, MMP1 and DNAH11). Six variants (ERAP1- p.Ile915Thr, ERAP2- p.Leu837Ser, COMT-p.His192Gln, CSAD-p.Pro418Ser, CDH1- p.Ala298Thr and CCR2-p.Met249Lys) led to destabilisation of protein structure as they had significant energy and residue interaction-related changes. We identified at least two mutations in 57% of patients, arguing in favour of a polygenic origin for the HELLP syndrome. Our results provide novel evidence regarding PE/HELLP's genetic origin, leading to new biomarkers, having potential clinical usefulness, being proposed.

Mid-gestational fetal placental blood flow is diminished in the fetus with congenital heart disease.

Data suggest fetuses with congenital heart disease (CHD) have placental abnormalities. Their abnormal placental vasculature may affect fetal placental blood flow, which has not previously been explored. We performed a retrospective cross-sectional study comparing umbilical venous volume flow (UVVF) of single ventricle, D-transposition of the great arteries, and tetralogy of Fallot fetuses with fetuses without CHD. UVVF and combined cardiac output (CCO) were calculated from fetal echocardiography and compared using t tests, χ2 and Fisher's exact tests. Mean gestational age and fetal weight were greater in CHD fetuses (26.5 weeks, 1119.4 g; n = 81, P < .001) compared to controls (23.1 weeks, 675 g; n = 170, P < .001). UVVF/fetal weight was nevertheless decreased among cases (99.8 vs 115.3 mL/min/kg, P < .001). Subgroup analysis of 20- to 25-week fetuses demonstrated no significant differences in case and control baseline characteristics. In CHD fetuses (n = 31) compared to controls (n = 144), absolute UVVF (50.8 vs 62.1 mL/min, P = .006), and UVVF/fetal weight (98.8 vs 118.5 mL/min/kg, P < .001) were decreased. Findings were similar in single ventricle (n = 24) and hypoplastic left heart syndrome (n = 14). Mid-gestational placental blood flow in CHD fetuses is decreased compared to controls. Further study is needed to explore the relationship between UVVF and placental pathology, and impact on outcomes.

Epigenetic signatures associated with maternal body mass index or gestational weight gain: a systematic review.

Maternal body mass index (BMI) and gestational weight gain (GWG) impacts both the mother's and the child's health, and epigenetic modifications have been suggested to mediate some of these effects in offspring. This systematic review aimed to summarize the current literature on associations between maternal BMI and GWG and epigenetic marks. We performed systematic searches in PubMed and EMBASE and manual searches of reference lists. We included 49 studies exploring the association between maternal BMI and/or GWG and DNA methylation or miRNA; 7 performed in maternal tissues, 13 in placental tissue and 38 in different offspring tissues. The most consistent findings were reported for the relationship between maternal BMI, in particular pre-pregnant BMI, and expression of miRNA Let-7d in both maternal blood and placental tissue, methylation of the gene HIF3A in umbilical cord blood and umbilical tissue, and with expression in the miR-210 target gene, BDNF in placental tissue and cord blood. Correspondingly, methylation of BDNF was also found in placental tissue and cord blood. The current evidence suggests that maternal BMI is associated with some epigenetic signatures in the mother, the placenta and her offspring, which could indicate that some of the effects proposed by the Developmental Origins of Health and Disease-hypothesis may be mediated by epigenetic marks. In conclusion, there is a need for large, well-designed studies and meta-analyses that can clarify the relationship between BMI, GWG and epigenetic changes.

Malaria in Pregnancy in Endemic Regions of Colombia: High Frequency of Asymptomatic and Peri-Urban Infections in Pregnant Women with Malaria.

Background Malaria in pregnancy (MiP) has been associated with adverse pregnancy outcomes. There is limited information on MiP in low transmission regions as Colombia. This study aimed to describe the epidemiology of MiP through active surveillance of infections by microscopy and polymerase chain reaction (PCR). Methods A cross-sectional study was conducted between May 2016 and January 2017 in five municipalities (Apartadó, Turbo, El Bagre, Quibdó, and Tumaco) in Colombia. Pregnant women self-presenting at health centers for antenatal care visits, seeking medical care for suspected malaria, or delivery, were enrolled. Diagnosis of Plasmodium spp was made in peripheral and placental blood samples by microscopy and PCR. Results A total of 787 pregnant women were enrolled; plasmodial infection was diagnosed by microscopy in 4.2% (95% CI 2.8-5.6; 33/787) or by nPCR in 5.3% (95% CI 3.8-6.9; 42/787) in peripheral blood. Most of the infections were caused by P. falciparum (78.5%), and 46% were afebrile (asymptomatic). Women in the first and second trimester of pregnancy were more likely to be infected (aOR = 3.06, 95%CI = 1.6 − 5.8). To live in the urban/peri-urban area (aOR = 3.04, 95%CI = 1.4 − 6.56), to have a history of malaria during last year (aOR = 5.45, 95%IC = 2.16 − 13.75), and the infrequent bed net usage (aOR = 2.8, 95%CI = 1.31 − 5.97) were associated with the infection. Pregnant infected women had a higher risk of anaemia (aOR = 2.18, 95%CI = 1.15 − 4.12) and fever (aOR = 14.2, 95%CI = 6.89 − 29.8). Conclusion The screening for malaria during antenatal care in endemic areas of Colombia is highly recommended due to the potential adverse effects of Plasmodium spp. infection in pregnancy and as an important activity for the surveillance of asymptomatic infections in the control of malaria.

Abnormal angiogenesis of placenta in progranulin‑deficient mice.

Progranulin (PGRN) is a secreted growth factor involved in pleiotropic functions, particularly angiogenesis. A distinctly different placental expression of PGRN has been reported between normal pregnancies and pregnancies with complications, such as pre-eclampsia or fetal growth restriction. However, the role of PGRN in placental vascular development remains to be elucidated. In the present study, PGRN-knockout mice (PGRN−/−) were used to investigate the role of PGRN in the development of placental blood vessels and placental formation. Placental weights and pup body weights were significantly lower in the PGRN−/− mice compared with the wild-type mice. Reduced labyrinthine layer areas and aberrant vascularization were also observed via hematoxylin and eosin staining of PGRN−/− mice at embryonic day 14.5 (E14.5) and E17.5. In addition, the morphological data obtained via immunohistochemistry, immunofluorescence staining and western blotting demonstrated decreased expression levels of the blood vessel markers α-smooth muscle actin and CD31 in PGRN−/− placentas. Furthermore, vasodilator endothelial nitric oxide synthase was reduced in the PGRN−/− placenta. These results indicated that PGRN serves an essential role in the normal angiogenesis of the placental labyrinth in mice.

Magnetic resonance imaging measurement of placental perfusion and oxygen saturation in early-onset fetal growth restriction.

ObjectiveWe hypothesised that a multi-compartment magnetic resonance imaging (MRI) technique that is sensitive to fetal blood oxygenation would identify changes in placental blood volume and fetal blood oxygenation in pregnancies complicated by early-onset fetal growth restriction (FGR).DesignCase–control study.SettingLondon, UK.PopulationWomen with uncomplicated pregnancies (estimated fetal weight [EFW] >10th centile for gestational age [GA] and normal maternal and fetal Doppler ultrasound, n = 12) or early- onset FGR (EFW <3rd centile with or without abnormal Doppler ultrasound <32 weeks GA, n = 12) were studied.MethodsAll women underwent MRI examination. Using a multicompartment MRI technique, we quantified fetal and maternal blood volume and feto-placental blood oxygenation.Main outcome measuresDisease severity was stratified according to Doppler pulsatility index and the relationship to the MRI parameters was investigated, including the influence of GA at scan.ResultsThe FGR group (mean GA 27+5 weeks, range 24+2 to 33+6 weeks) had a significantly lower EFW compared with the control group (mean GA 29+1 weeks; –705 g, 95% CI –353 to –1057 g). MRI-derived feto-placental oxygen saturation was higher in controls compared with FGR (75 ± 9.6% versus 56 ± 16.2%, P = 0.02, 95% CI 7.8–30.3%). Feto-placental oxygen saturation estimation correlated strongly with GA at scan in controls (r = –0.83).ConclusionUsing a novel multimodal MRI protocol we demonstrated reduced feto-placental blood oxygen saturation in pregnancies complicated by early-onset FGR. The degree of abnormality correlated with disease severity defined by ultrasound Doppler findings. Gestational age-dependent changes in oxygen saturation were also present in normal pregnancies.

Maternal Fetal Health

Maternal Fetal Health

Is extra-embryonic endoderm a source of placental blood cells?

The extra-embryonic hypoblast/visceral endoderm of Placentalia carries out a variety of functions during gestation, including hematopoietic induction. Results of decades-old and recent experiments have provided compelling evidence that, in addition to its inducing properties, hypoblast/visceral endoderm itself is a source of placental blood cells. Those observations that highlight extra-embryonic endoderm's role as an overlooked source of placental blood cells across species are briefly discussed here, with suggestions for future exploration.

Volume blood flow-based indices of fetal brain sparing in the second half of pregnancy: A longitudinal study.

Cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) are clinically used as a measure of fetal brain sparing. These are calculated as the ratios between the pulsatility indices (PIs) of middle cerebral (MCA) and umbilical (UA) arteries, and are an indirect representation of the balance between cerebral and placental perfusion. Volume blood flow (Q)-based ratios, ie Q-CPR or Q-UCR, would directly reflect the distribution of fetal cardiac output to the placenta and brain. Thus, we aimed to determine the development pattern of Q-CPR and Q-UCR during the second half of pregnancy, construct reference intervals, and evaluate their association with CPR and UCR. In a longitudinal cohort study of low-risk pregnancies, the inner diameter of the fetal superior vena cava (SVC) and umbilical vein (UV) was measured and velocity waveforms were obtained from the MCA, UA, UV and SVC using ultrasound at approximately 4-weekly intervals from 20 to 41weeks. The CPR was calculated as PIMCA /PIUA and the inverse ratio was the UCR. Cerebral and placental blood flows were estimated as the product of mean velocity and cross-sectional area of the SVC and UV, respectively. Q-CPR was calculated as QSVC /QUV and the inverse as the Q-UCR. Gestational age-specific reference intervals were calculated and associations between variables were tested using multilevel regression modeling. Longitudinal reference intervals of Q-CPR and Q-UCR were established based on 471 paired measurements of QSVC and QUV obtained serially from 134 singleton pregnancies. The mean Q-CPR increased from 0.4 to 0.8 during the second half of pregnancy and Q-UCR declined from 2.5 to 1.3, while the CPR and UCR had U-shaped curves but in opposite directions. No significant correlation was found between CPR and Q-CPR (R=0.10; P=.051), or UCR and Q-UCR (R=0.09; P=.11), and the agreement between PI-based and Q-based indices of fetal brain sparing was poor. Indices of fetal brain sparing based on placental and cerebral volume blood flow differ from those calculated from UA and MCA PIs. They correlated poorly with conventional CPR and UCR, indicating that they may provide additional/different physiological information. Reference values of Q-CPR and Q-UCR established here can be useful to investigate their clinical value further.

Maternity health professionals\u2019 perspectives of cord clamp timing, cord blood banking and cord blood donation: a qualitative study

BackgroundParents today have several options for the management of their infant’s cord blood during the third stage of labour. Parents can choose to have their infant’s cord clamped early or to have deferred cord clamping. If the cord is clamped early, cord blood can be collected for private cord blood banking or public cord blood donation for use later if needed. If cord clamping is deferred, the placental blood physiologically transfuses to the neonate and there are physiological advantages to this. These benefits include a smoother cardiovascular transition and increased haemoglobin levels while not interfering with the practice of collecting cord blood for gases if needed. The aim of this study is to explore Australian maternity health professionals’ perspectives towards cord clamp timing, cord blood banking and cord blood donation.MethodsFourteen maternity health professionals (midwives and obstetricians) from both private and public practice settings in Australia participated in semi-structured interviews either in person or by telephone. Interviews were transcribed and data analysed using thematic analysis.ResultsOverall there was strong support for deferred cord clamping, and this was seen as important and routinely discussed with parents as part of antenatal care. However, support did not extend to the options of cord blood banking and donation and to routinely informing parents of these options even when these were available at their birthing location.ConclusionFormalised education for maternity health professionals is needed about the benefits and implications of cord blood banking and cord blood donation so that they have the confidence to openly discuss all options of cord clamp timing, cord blood banking and cord blood donation to facilitate informed decision-making by parents.

Decidual Vasculopathy Identification in Whole Slide Images Using Multiresolution Hierarchical Convolutional Neural Networks

After a child is born, the examination of the placenta by a pathologist for abnormalities, such as infection or maternal vascular malperfusion, can provide important information about the immediate and long-term health of the infant. Detection of the pathologic placental blood vessel lesion decidual vasculopathy (DV) has been shown to predict adverse pregnancy outcomes, such as preeclampsia, which can lead to mother and neonatal morbidity in subsequent pregnancies. However, because of the high volume of deliveries at large hospitals and limited resources, currently a large proportion of delivered placentas are discarded without inspection. Furthermore, the correct diagnosis of DV often requires the expertise of an experienced perinatal pathologist. We introduce a hierarchical machine learning approach for the automated detection and classification of DV lesions in digitized placenta slides, along with a method of coupling learned image features with patient metadata to predict the presence of DV. Ultimately, the approach will allow many more placentas to be screened in a more standardized manner, providing feedback about which cases would benefit most from more in-depth pathologic inspection. Such computer-assisted examination of human placentas will enable real-time adjustment to infant and maternal care and possible chemoprevention (eg, aspirin therapy) to prevent preeclampsia, a disease that affects 2% to 8% of pregnancies worldwide, in women identified to be at risk with future pregnancies.

Association of Maternal Factors and HIV Infection With Innate Cytokine Responses of Delivering Mothers and Newborns in Mozambique.

Maternal factors and exposure to pathogens have an impact on infant health. For instance, HIV exposed but uninfected infants have higher morbidity and mortality than HIV unexposed infants. Innate responses are the first line of defense and orchestrate the subsequent adaptive immune response and are especially relevant in newborns. To determine the association of maternal HIV infection with maternal and newborn innate immunity we analyzed the cytokine responses upon pattern recognition receptor (PRR) stimulations in the triad of maternal peripheral and placental blood as well as in cord blood in a cohort of mother-infant pairs from southern Mozambique. A total of 48 women (35 HIV-uninfected and 13 HIV-infected) were included. Women and infant innate responses positively correlated with each other. Age, gravidity and sex of the fetus had some associations with spontaneous production of cytokines in the maternal peripheral blood. HIV-infected women not receiving antiretroviral therapy (ART) before pregnancy showed decreased IL-8 and IL-6 PRR responses in peripheral blood compared to those HIV-uninfected, and PRR hyporesponsiveness for IL-8 was also found in the corresponding infant’s cord blood. HIV infection had a greater impact on placental blood responses, with significantly increased pro-inflammatory, TH1 and TH17 PRR responses in HIV-infected women not receiving ART before pregnancy compared to HIV-uninfected women. In conclusion, innate response of the mother and her newborn was altered by HIV infection in the women who did not receive ART before pregnancy. As these responses could be related to birth outcomes, targeted innate immune modulation could improve maternal and newborn health.

Comparison of Vascular Responses to Vasoconstrictors in Human Placenta in Preeclampsia between Preterm and Later Term.

Placental blood vessels play important roles in maternal-fetal circulation. Although pathologic mechanisms of preeclampsia are unclear, it is known that placental vascular dysfunction could contribute to pregnant hypertension. However, placental micro-vessel function or dysfunction at preterm has not been investigated. Human placentas from normal and preeclamptic pregnancies at preterm and term were obtained. Placental micro-vessels were used for determining vascular tension and responses to various vasoconstrictors as well as intracellular calcium store capability. It was the first time to show vascular responses in placental arteries to angiotensin II, endothelin-1, and other vascular drugs at preterm. Compared to the control, placental vascular contractile responses to angiotensin II and caffeine were significantly decreased, while placental vascular responses to KCl, endothelin-1, and bradykinin were not significantly altered in the later term group in preeclampsia. In comparison of placental micro-vessel tension between the preterm and later term, caffeine- and serotonin-induced vascular contractions were significantly weaker in the preterm than that in the later term. On the contrary, vascular response to angiotensin II was increased in the preterm preeclampsia, while KCl-, endothelin-1, and bradykinin-mediated placental vessel responses in the preterm preeclampsia were similar to that in later term preeclampsia. New data showed that micro-vessel responses to angiotensin II and serotonin, not endothelin- 1 or bradykinin, were significantly reduced in the human placentas at preterm, and intracellular Ca2+ store capacity was damaged too, providing important information on possible contributions of placental vascular dysfunction to pregnant hypertension.

The impact of gravidity, symptomatology and timing of infection on placental malaria

BackgroundPlacental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria.MethodsThe aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitaemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection.ResultsOf the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34–18.2, p < 0.001), and each episode of malaria was associated with over a twofold increase in placental malaria (aOR 2.35, 95% CI 1.69–3.26, p < 0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02–1.27, p = 0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23–28.43, p < 0.001).ConclusionsTotal number of P. falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were more frequently identified in those with placental malaria, whereas in multigravidas, parasitaemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.

Elimination of \u201ckitome\u201d and \u201csplashome\u201d contamination results in lack of detection of a unique placental microbiome

BackgroundA placental microbiome, which may be altered in gestational diabetes mellitus (GDM), has been described. However, publications raising doubts about the existence of a placental microbiome that is different than contaminants in DNA extraction kits and reagents (“kitomes”) have emerged. The aims of this study were to confirm the existence of a placental microbiome distinct from contaminants and determine if it is altered in GDM mothers.ResultsWe first enrolled normal weight, obese and GDM mothers (N = 17) at term elective cesarean section delivery in a pilot case control study. Bacterial DNA was extracted from placental parenchyma, maternal and cord blood, maternal vaginal-rectal swabs, and positive and negative controls with the standard Qiagen/MoBio Power Soil kit. Placentas had significantly higher copies of bacterial 16S rRNA genes than negative controls, but the placental microbiome was similar in all three groups and could not be distinguished from contaminants in blank controls. To determine the source and composition of the putative placental bacterial community identified in the pilot study, we expanded the study to 10 subjects per group (N = 30) and increased the number and variety of negative controls (N = 53). We modified our protocol to use an ultraclean DNA extraction kit (Qiagen QIAamp UCP with Pathogen Lysis Tube S), which reduced the “kitome” contamination, but we were still unable to distinguish a placental microbiome from contaminants in negative controls. We noted microbial DNA from the high biomass vaginal-rectal swabs and positive controls in placental and negative control samples and determined that this resulted from close proximity well-to-well cross contamination or “splashome”. We eliminated this source of contamination by repeating the sequencing run with a minimum of four wells separating high biomass from low biomass samples. This reduced the reads of bacterial 16S rRNA genes in placental samples to insignificant numbers.ConclusionsWe identified the problem of well-to-well contamination (“splashome”) as an additional source of error in microbiome studies of low biomass samples and found a method of eliminating it. Once “kitome” and “splashome” contaminants were eliminated, we were unable to identify a unique placental microbiome.

Toxoplasmosis congénita en gemelos

Congenital toxoplasmosis in twin pregnancies is infrequent. We present the case of a monozygotic and monocorial twin pregnancy with maternal toxoplasmosis infection diagnosed at 33 weeks gestation by detecting reactive IgM and IgG and low avidity test for IgG. The detection of the parasite in amniotic fluid could not be performed because the amniocentesis was not done. The term newborns presented cerebral calcifications and bilateral active chorioretinitis without other associated clinical manifestations. They had IgG and IgM reactive for toxoplasmosis. The detection of Toxoplasma gondii was not performed by placental PCR or cord blood. They received treatment during the first year of life with pyrimethamine, sulfadiazine and folinic acid. They had no adverse events associated with the therapy. The diagnostic assessment and treatment does not differ from pregnancies with a single fetus. One or both newborns may be compromised. Multidisciplinary monitoring is essential for the early detection of reactivations or progression of lesions.

Long noncoding RNA SNHG12 promotes the proliferation, migration, and invasion of trophoblast cells by regulating the epithelial-mesenchymal transition and cell cycle.

ObjectiveThe deficient placental blood perfusion caused by the attenuated infiltration of trophoblast cells is a key factor in the occurrence of preeclampsia (PE). Furthermore, the long noncoding (lnc)RNA SNHG12 (small nucleolar RNA host gene 12) can promote the proliferation and metastasis of multiple tumor cells. However, whether lncRNA SNHG12 affects proliferation and metastasis of trophoblast cells is unclear.MethodsWe examined the level of lncRNA SNHG12 in plasma and placenta of patients with PE and constructed trophoblast cells with overexpressed or knocked down SNHG12. CCK-8, wound healing, and Transwell assays were used to detect alterations in proliferation, migration, and invasion of trophoblast cells. Western blotting was used to detect proteins related to the epithelial–mesenchymal transition (EMT), and cell cycle assays clarified cell cycle distribution.ResultsLncRNA SNHG12 promoted the proliferation, migration, and invasion of trophoblast cells. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, β-catenin, and vimentin were positively correlated with SNHG12, and expression of E-cadherin was negatively correlated with SNHG12. SNHG12 also promoted the transition of trophoblast cells from G0/G1 to S phase.ConclusionOverall, lncRNA SNHG12 promoted the migration and invasion of trophoblast cells by inducing the progression of EMT.

NO placental inflammation.

NO placental inflammation.