scholarly journals Proteomic identification of membrane-associated placental protein 4 (MP4) as perlecan and characterization of its placental expression in normal and pathologic pregnancies

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6982 ◽  
Author(s):  
Nikolett Lilla Szenasi ◽  
Eszter Toth ◽  
Andrea Balogh ◽  
Kata Juhasz ◽  
Katalin Karaszi ◽  
...  
Keyword(s):  
Hellp Syndrome ◽  
Core Protein ◽  
Placental Tissue ◽  
First Trimester ◽  
Virtual Microscopy ◽  
Third Trimester ◽  
Diagnostic Significance ◽  
Ischaemic Injury ◽  
Tissue Samples ◽  
Placental Protein

BackgroundMore than 50 human placental proteins were isolated and physico-chemically characterized in the 70–80s by Hans Bohn and co-workers. Many of these proteins turned to have important role in placental functions and diagnostic significance in pregnancy complications. Among these proteins was membrane-associated placental protein 4 (MP4), for which identity or function has not been identified yet. Our aim was to analyze the sequence and placental expression of this protein in normal and complicated pregnancies including miscarriage, preeclampsia and HELLP syndrome.MethodsLyophilized MP4 protein and frozen healthy placental tissue were analyzed using HPLC-MS/MS. Placental tissue samples were obtained from women with elective termination of pregnancy (first trimester controls,n= 31), early pregnancy loss (EPL) (n= 13), early preeclampsia without HELLP syndrome (n= 7) and with HELLP syndrome (n= 8), late preeclampsia (n= 8), third trimester early controls (n= 5) and third trimester late controls (n= 9). Tissue microarrays were constructed from paraffin-embedded placentas (n= 81). Slides were immunostained with monoclonal perlecan antibody and evaluated using light microscopy and virtual microscopy. Perlecan was also analyzed for its expression in placentas from normal pregnancies using microarray data.ResultsMass spectrometry-based proteomics of MP4 resulted in the identification of basement membrane-specific heparan sulfate proteoglycan core protein also known as perlecan. Immunohistochemistry showed cytoplasmic perlecan localization in syncytiotrophoblast and cytotrophoblasts of the villi. Perlecan immunoscore decreased with gestational age in the placenta. Perlecan immunoscores were higher in EPL compared to controls. Perlecan immunoscores were higher in early preeclampsia without and with HELLP syndrome and lower in late preeclampsia than in respective controls. Among patients with preeclampsia, placental perlecan expression positively correlated with maternal vascular malperfusion and negatively correlated with placental weight.ConclusionOur findings suggest that an increased placental perlecan expression may be associated with hypoxic ischaemic injury of the placenta in miscarriages and in early preeclampsia with or without HELLP syndrome.

scholarly journals Immunoreactive adrenomedullin (AM) concentration in maternal plasma during human pregnancy and AM expression in placenta

2000 ◽  
pp. 683-687 ◽  
Author(s):  
K Kobayashi ◽  
T Kubota ◽  
T Aso ◽  
Y Hirata ◽  
T Imai ◽  
...  
Keyword(s):  
Northern Blot Analysis ◽  
Plasma Concentrations ◽  
Placental Tissue ◽  
First Trimester ◽  
Maternal Plasma ◽  
Placental Lactogen ◽  
Third Trimester ◽  
Maternal Circulation ◽  
The Third ◽  
System A

Adrenomedullin (AM) is a novel vasorelaxant peptide, isolated from human pheochromocytoma. Although AM may be involved in the regulation of the cardiovascular system, a number of other mechanisms are also involved. The present study was undertaken to confirm the presence of AM in human maternal circulation and in placental function during pregnancy. Immunoreactive (ir) AM concentrations in maternal plasma were 3.4+/-0.7fmol/ml (mean+/-s.e. m.) in the first trimester, 3.3+/-1.1fmol/ml in the second trimester, 7.3+/-2.8fmol/ml in the third trimester, 4.1+/-1.9fmol/ml in early puerperium and 3.0+/-0.4fmol/ml in non-pregnant periods; the concentration in the third trimester was significantly greater than those in other periods. Plasma concentrations of estradiol (E(2)), progesterone, human placental lactogen (hPL) and human chorionic gonadotropin (hCG) were also measured, using RIA kits. Significant correlations have been demonstrated between the concentrations of irAM and those of E(2), progesterone and hPL. We therefore examined the expression of AM within the placental tissues using immunohistochemistry and northern blot analysis in order to demonstrate a correlation between the presence of AM in the placenta and maternal plasma. Using immunohistochemistry, we detected AM in the amnion at term and the expression of AM mRNA in human placental tissues using cloned human (h) AM complementary DNA as a probe. This study demonstrates the immunoreactivity of human hAM in maternal plasma during pregnancy, and suggests that hAM in maternal plasma is generated partly from placental tissue.

Severe Reduction of Free ADAMTS13, Unbound to Von Willebrand Factor, in Plasma Milieu Is a Unique Feature of HELLP Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 134-134
Author(s):  
Yoko Yoshida ◽  
Ayami Isonishi ◽  
Toshiyuki Sado ◽  
Masaki Hayakawa ◽  
Hideo Yagi ◽  
...  
Keyword(s):  
Shear Stress ◽  
Pregnant Women ◽  
Hellp Syndrome ◽  
First Trimester ◽  
Normal Pregnancy ◽  
High Shear ◽  
High Shear Stress ◽  
Third Trimester ◽  
Severe Reduction ◽  
Mild Reduction

Abstract Introduction Plasma ADAMTS13 exists at least two forms, bound and unbound to vonWillebrandfactor (VWF), of which the former was assumed to be 3% of the total by the immunoprecipitation method (Feyset al., JTH 2009). We have shown that plasma ADAMTS13 consists of 3 group bands, by means of isoelectric focusing (IEF) analysis (Hori et al, Transfusion 2013). Band I (pI4.9-5.6) was assumed to be free ADAMTS13, unbound to VWF, and Band III (pI7.0-7.5) was a complex with high-molecular-weight VWFmultimers(HMW-VWFM). However, the feature of Band II (pI5.8-6.7) was undetermined. HELLP (hemolysis, elevated liver enzymes and low platelet counts) syndrome is a life-threatening thromboembolic complication during pregnancy, and its pathogenesis is not determined. The curative therapy of HELLP syndrome is a termination of pregnancy. It was reported that plasma VWF antigen (VWF: Ag) was remarkably increased (215-422% of the normal) with a mild reduction of ADAMTS13 activity (ADAMTS13: AC) (12-43 % of the normal), but without qualitative analysis of ADAMTS13 antigen (Lattuadaet al.,Haematologica2003). We here analyzed plasma ADAMTS13 antigen in 9 patients with HELLP syndrome using the IEF gel, and revealed a unique picture of severe reduction of Band I (free ADAMTS13), unbound to VWF, that was not seen in plasmas from normal pregnancy. Patients and Methods One hundred twenty-nine normal pregnant women and 9 patients with HELLP syndrome were analyzed under approval by the ethics committees of Nara Medical University. All individuals gave written informed consent to the study. Diagnosis of HELLP syndrome was made by all the following laboratory abnormalities: characteristics peripheral blood smear, serum LDH >600 IU/L (or total bilirubin >1.2 mg/dL), AST >70 IU/L, and platelet counts < 100,000/mm3 (Sibai et al., Am JObstetGynecol 1993). Plasma level of ADAMTS13: AC was determined by chromogenic ADAMTS13-act-ELISA, and VWF: Ag was measured by a sandwich ELISA using a rabbit polyclonal anti-human VWF antibody. As reported previously (Hori et al., Transfusion 2013), the IEF was performed using a large-pore agarose-acrylamide composing gel followed by detection with anti-ADAMTS13 monoclonal antibody. Results In normal women, plasma levels of VWF: Agweremarkedly increased during pregnancy, and the values of third trimester (median 223%) were almost two times higher than those of first trimester (119%). Contrarily,plasma levels ofADAMTS13: AC were significantly decreased in second (68.4%) and third (66.2%) trimester compared with first trimester (84.3%, p<0.01 and p<0.001, respectively). Of note, a reduction in ADAMTS13: AC was significantly prolonged in postpartum period (50.2%, p<0.001), while increased VWF: Ag was rapidly recovered after delivery. Further, the IEF analysis of normal pregnant women showed that Band I was slightly decreased in accord with progression of pregnancy. In puerperium, there was no difference in ADAMTS13: AC between normal pregnant women and patients with HELLP syndrome. However, the values of VWF: Ag of patients with HELLP syndrome (352%) were significantly higher than those of normal pregnant women (178%, p<0.001), in agreement with a previous report. Interestingly, however, here we have shown that 7 out of 9 patients with HELLP syndrome showed severe reduction of Band I in puerperium period by the IEF analysis of ADAMTS13 (Figure). Discussion In normal pregnant women, the decreased ADAMTS13:AC was assumed to reflect a consumption of the enzyme for cleavage of increased VWF. Interestingly, both Band II and III were almost unchanged during normal pregnancy, but Band I slightly decreased in third trimester, concomitantly with a mild reduction of ADAMTS13:AC. In contrast, Band I was severely reduced during the acute phase of HELLP syndrome in 7 out of 9 patients. Our previous report indicated that under high-shear-stress Band I inhibited the VWF-dependent platelet aggregation in a dose-response manner from the initial phase, whereas Band III (+II) worked from the later phase. This result indicates that ADAMTS13 lacking Band I neither readily binds to VWF nor efficiently blocks the heightened high-shear-stress induced platelet aggregation generated by newly produced HMW-VWFM. Our data suggest that ADAMTS13 preparation might be used as a therapeutic option for the treatment of HELLP syndrome, before termination of pregnancy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Calcifediol Decreases Interleukin-6 Secretion by Cultured Human Trophoblasts From GDM Pregnancies

2019 ◽  
Vol 3 (11) ◽  
pp. 2165-2178 ◽  
Author(s):  
Marilyn Lacroix ◽  
Farah Lizotte ◽  
Marie-France Hivert ◽  
Pedro Geraldes ◽  
Patrice Perron
Keyword(s):  
Vitamin D ◽  
Placental Tissue ◽  
Target Cells ◽  
Compensatory Mechanism ◽  
Tissue Samples ◽  
Diet And Exercise ◽  
Protein Expressions ◽  
Placental Protein ◽  
Nongenomic Effects ◽  
Inflammatory Effect

Abstract Gestational diabetes mellitus (GDM) is often characterized by low maternal calcifediol (25OHD) and high inflammation levels. This study aimed to determine whether placental protein expressions of CYP27B1, vitamin D receptor (VDR), and CYP24A1 are impaired in GDM and to investigate the effect of a 25OHD treatment on IL-6 secretion by GDM trophoblasts compared with normoglycemic (NG) trophoblasts. Placental tissue samples were harvested to determine protein expression of CYP27B1, VDR, and CYP24A1 by immunoblots. Isolated trophoblasts were stimulated with 25OHD concentrations (25 to 2000 nM) once a day for 3 days and IL-6 secretion was quantified (ELISA). We recruited 17 NG women, 19 women with GDM treated with diet and exercise alone (GDM-d) and 9 women with GDM who necessitated insulin therapy (GDM-i). Protein expressions of CYP27B1 and VDR were significantly higher in placental tissue from GDM-d women compared with NG women (both P = 0.02), whereas no differences were detected between GDM-i and NG placental tissues. In cultured trophoblasts (two groups; n = 5 NG and n = 5 GDM-d), exposure to increasing 25OHD concentrations significantly decreased IL-6 secretion in the GDM-d group only (P = 0.006). After treatment with 25OHD (2000 nM), IL-6 secretion was lower in the GDM-d group compared with the NG group (P = 0.03). Our results suggest an upregulation of the VDR-1,25(OH)2D complex bioavailability in GDM-d placentas, possibly reflecting a compensatory mechanism aiming to ensure that vitamin D can exert its genomic and nongenomic effects in the target cells of the placental-fetal unit. Our findings support an anti-inflammatory effect of vitamin D at the feto-maternal interface in GDM-d pregnancies.

Avipoxvirus detected in tumor-like lesions in a white-faced whistling duck (Dendrocygna viduata)

2020 ◽  
Vol 40 (10) ◽  
pp. 818-823
Author(s):  
Juliana F.V. Braga ◽  
Rodrigo M. Couto ◽  
Marcelo C. Rodrigues ◽  
Roselene Ecco
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phylogenetic Analysis ◽  
Protein Gene ◽  
Core Protein ◽  
Avian Species ◽  
Tissue Samples ◽  
Histopathological Evaluation ◽  
In Captivity ◽  
Avian Pox ◽  
Tumor Like Lesions

ABSTRACT: Avipoxvirus is the etiological agent of the avian pox, a well-known disease of captive and wild birds, and it has been associated with tumor-like lesions in some avian species. A white-faced whistling duck (Dendrocygna viduata) raised in captivity was referred to a Veterinary Teaching Hospital in Northeast due to cutaneous nodules present in both wings. A few days after the clinical examination, the animal died naturally. Once submitted to necropsy, histopathological evaluation of the lesions revealed clusters of proliferating epithelial cells expanding toward the dermis. Some of these cells had round, well-defined, intracytoplasmic eosinophilic material suggestive of poxvirus inclusion (Bollinger bodies). PCR performed on the DNA extracted from tissue samples amplified a fragment of the 4b core protein gene (fpv167), which was purified and sequenced. This fragment of Avipoxvirus DNA present in these tumor-like lesions showed high genetic homology (100.0%) with other poxviruses detected in different avian species in several countries, but none of them were related to tumor-like lesions or squamous cell carcinoma. This is the first report of Avipoxvirus detected in tumor-like lesions of a white-faced whistling duck with phylogenetic analysis of the virus.

Correlations Between the Values of Maternal Glycemia from the Last Trimester of Pregnancy and Fetal Birth Weight

2013 ◽  
Vol 20 (3) ◽  
pp. 259-265
Author(s):  
Monica Vereş ◽  
Aurel Babeş ◽  
Szidonia Lacziko
Keyword(s):  
First Trimester ◽  
Mean Value ◽  
Fetal Macrosomia ◽  
Entire Group ◽  
Third Trimester ◽  
The Third ◽  
Group I ◽  
Fetal Birth Weight ◽  
First Trimester Of Pregnancy ◽  
The Mean

Abstract Background and aims: Gestational diabetes represents a form of diabetes diagnosed during pregnancy that is not clearly overt diabetes. In the last trimester of gestation the growth of fetoplacental unit takes place, thus maternal hyperglycemia will determine an increased transplacental passage, hyperinsulinemia and fetal macrosomia. The aim of our study was that o analyzing the effect of maternal glycemia from the last trimester of pregnancy over fetal weight. Material and method: We run an observational study on a group of 46 pregnant women taken into evidence from the first trimester of pregnancy, separated in two groups according to blood glucose determined in the third trimester (before birth): group I normoglycemic and group II with hyperglycemia (>92mg/dl). Results: The mean value of third trimester glycemia for the entire group was of 87.13±22.03. The mean value of the glycemia determined in the third trimester of pregnancy was higher in the second group (109.17 mg/dl) in comparison to the first group (74.,21 mg/dl). The ROC curve for third trimester glycemia as fetal macrosomia appreciation test has an AUC of 0.517. Conclusions: Glycemia determined in the last trimester of pregnancy cannot be used alone as the predictive factor for fetal macrosomia.

scholarly journals Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

2000 ◽  
Vol 165 (3) ◽  
pp. 669-677 ◽  
Author(s):  
O Vakkuri ◽  
SS Arnason ◽  
A Pouta ◽  
O Vuolteenaho ◽  
J Leppaluoto
Keyword(s):  
Pregnant Women ◽  
Human Plasma ◽  
High Performance ◽  
Chemical Nature ◽  
Solid Phase ◽  
Plasma Concentrations ◽  
First Trimester ◽  
Plasma Samples ◽  
Third Trimester ◽  
Endogenous Substances

Ouabain was recently isolated from human plasma, bovine hypothalamus and bovine adrenal in attempts to identify endogenous substances inhibiting the cell membrane sodium pump. A number of radioimmunoassays have been developed in order to study the clinical significance of ouabain. The results have been controversial with regard to the presence and chemical nature of plasma ouabain-like immunoreactivity. We have now measured ouabain in healthy and pregnant individuals using solid-phase extraction of plasma samples followed by a new radioimmunoassay with the extraordinary sensitivity of at least 2 fmol/tube (5 pmol/l). Plasma extracts, a previously isolated human plasma ouabain-like compound and bovine hypothalamic inhibitory factor displaced the tracer in parallel and eluted identically with ouabain in high-performance liquid chromatography. Plasma ouabain immunoreactivity was found to be much lower than reported previously: 12.6+/-1.3 pmol/l in healthy men (mean+/-s.e., n=20) and 9.4+/-0.7 pmol/l in women (n=14). In pregnant women (n=28) plasma ouabain concentration was 16.3+/-4.0 pmol/l during the first trimester, 18.8+/-4.3 pmol/l during the second trimester and 24.3+/-4.0 pmol/l during the third trimester (all P<0.01 compared with non-pregnant women). Plasma ouabain 3-5 days after the delivery was 13.6+/-1.1 pmol/l (n=10, P<0.05-0.01 compared with second and third trimesters). The pregnancy-related changes in the plasma concentrations of ouabain resembled those of cortisol. Therefore cortisol was measured from the same plasma samples and a significant positive correlation was found (r=0.512, P=0.006). The similar profiles of plasma ouabain and cortisol during pregnancy and their rapid decreases postpartum are consistent with the adrenal cortical origin of ouabain and also show that the secretions of these hormones are possibly under the control of same factors.

scholarly journals Maternal bisphenol urine concentrations, fetal growth and adverse birth outcomes: A population-based prospective cohort

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chalana M. Sol ◽  
Charissa van Zwol - Janssens ◽  
Elise M. Philips ◽  
Alexandros G. Asimakopoulos ◽  
Maria-Pilar Martinez-Moral ◽  
...  
Keyword(s):  
Birth Outcomes ◽  
Fetal Growth ◽  
Head Circumference ◽  
Lower Risk ◽  
First Trimester ◽  
Population Based ◽  
Third Trimester ◽  
Bisphenol S ◽  
Fetal Head ◽  
Urine Concentrations

Abstract Background Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods. Methods In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth. Results An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth. Conclusions Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.

scholarly journals Trastuzumab administration during pregnancy: un update

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Angeliki Andrikopoulou ◽  
Kleoniki Apostolidou ◽  
Spyridoula Chatzinikolaou ◽  
Garyfalia Bletsa ◽  
Eleni Zografos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
First Trimester ◽  
Systemic Review ◽  
Third Trimester ◽  
Her2 Positive ◽  
Exact Test ◽  
Metastatic Setting ◽  
Epidermal Growth

Abstract Background Over than one third (28–58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome. Methods Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words “breast”, “cancer”, “trastuzumab” and “pregnancy”. This study was performed in accordance with the PRISMA guidelines. Results A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1–32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher’s exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy. Conclusions Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.

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