scholarly journals Circulating Placental Alkaline Phosphatase Expressing Exosomes in Maternal Blood Showed Temporal Regulation of Placental Genes

2021 ◽  
Vol 8 ◽  
Author(s):  
Arshiya Parveen ◽  
Suman Mishra ◽  
Medha Srivastava ◽  
Dharmendra K. Chaudhary ◽  
Deepa Kapoor ◽  
...  

Background: Analysis of placental genes could unravel maternal-fetal complications. However, inaccessibility to placental tissue during early pregnancy has limited this effort. We tested if exosomes (Exo) released by human placenta in the maternal circulation harbor crucial placental genes.Methods: Placental alkaline phosphate positive exosomes (ExoPLAP) were enriched from maternal blood collected at the following gestational weeks; 6–8th (T1), 12–14th (T2), 20–24th (T3), and 28th−32nd (T4). Nanotracking analysis, electron microscopy, dynamic light scattering, and immunoblotting were used for characterization. We used microarray for transcriptome and quantitative PCR (qPCR) for gene analysis in ExoPLAP.Results: Physical characterization and presence of CD63 and CD9 proteins confirmed the successful ExoPLAP enrichment. Four of the selected 36 placental genes did not amplify in ExoPLAP, while 32 showed regulations (n = 3–8/time point). Most genes in ExoPLAP showed significantly lower expression at T2–T4, relative to T1 (p < 0.05), such as NOS3, TNFSF10, OR5H6, APOL3, and NEDD4L. In contrast, genes, such as ATF6, NEDD1, and IGF2, had significantly higher expression at T2–T4 relative to T1. Unbiased gene profiling by microarray also confirmed expression of above genes in ExoPLAP-transcriptome. In addition, repeated measure ANOVA showed a significant change in the ExoPLAP transcriptome from T2 to T4 (n = 5/time point).Conclusion: Placental alkaline phosphate positive exosomes transcriptome changed with gestational age advancement in healthy women. The transcriptome expressed crucial placental genes involved in early embryonic development, such as actin cytoskeleton organization, appropriate cell positioning, DNA replication, and B-cell regulation for protecting mammalian fetuses from rejection. Thus, ExoPLAP in maternal blood could be a promising source to study the placental genes regulation for non-invasive monitoring of placental health.

2021 ◽  
pp. 109352662199902
Author(s):  
Stephanie Shea ◽  
Alberto Paniz-Mondolfi ◽  
Emilia Sordillo ◽  
Michael Nowak ◽  
Fumiko Dekio

Bacillus cereus is a gram-positive, rod-shaped bacterium that is commonly implicated in foodborne illness but has also become increasingly recognized as a source of serious non-gastrointestinal infections, including sepsis, meningitis, and pneumonia. Non-gastrointestinal B. cereus infections have been identified in children, especially in neonates; however, there are no previously described cases of fetal demise associated with B. cereus placental infection. We present a case of acute chorioamnionitis-related intrauterine fetal demise of twin A at 17 weeks gestation, noted two days after selective termination of twin B. Histological examination revealed numerous gram-positive bacilli in placental tissue, as well as fetal vasculature, in the setting of severe acute necrotizing chorioamnionitis and subchorionitis, intervillous abscesses, acute villitis, and peripheral acute funisitis. Cultures of maternal blood and placental tissue both yielded growth of B. cereus. This case underscores the importance of B. cereus as a human pathogen, and specifically demonstrates its potential as an agent of severe intraamniotic and placental infection with poor outcomes for the fetus.


1981 ◽  
Vol 50 (5) ◽  
pp. 999-1005 ◽  
Author(s):  
J. Qvist ◽  
R. E. Weber ◽  
W. M. Zapol

Oxygen equilibria of whole blood and hemoglobins from adult and fetal Weddell seals are reported. The maternal blood shows a lower O2 affinity than the fetal blood (halfsaturation O2 tension P50 = 26.9 +/- 1.18 and 21.4 +/- 1.25 Torr, respectively, at 37 degrees C and pH 7.4), and a greater Bohr effect (delta log P50/delta pH = -0.49 and -0.31, respectively, at pH 7.4-6.8), correlated with higher red cell 2,3-diphosphoglycerate (2,3-diphosphoglycerate (2,3-DPG) concentrations (6.45 +/- 0.81 mmol.1-1, compared to 2.65 +/- 0-42 mmol.1-1 in the fetus). Both the maternal and fetal erythrocytes contain two major and two minor hemoglobin components occurring in the same ratio and the 2,3-DPG-free whole hemolysates, as well as the isolated major components from each stage, show the same oxygenation properties, ascribing the whole-blood differences to the higher adult DPG levels. A 2,3-DPG effect also appears to account for the disparity in the Bohr effects, which will favor unloading of O2 from the maternal circulation during diving as maternal and fetal blood pH decrease in parallel.


2018 ◽  
Vol 132 (12) ◽  
pp. 1215-1242 ◽  
Author(s):  
Vardaman M. Buckalew

Endogenous digitalis-like factor(s), originally proposed as a vasoconstrictor natriuretic hormone, was discovered in fetal and neonatal blood accidentally because it cross-reacts with antidigoxin antibodies (ADAs). Early studies using immunoassays with ADA identified the digoxin-like immuno-reactive factor(s) (EDLF) in maternal blood as well, and suggested it originated in the feto–placental unit. Mammalian digoxin-like factors have recently been identified as at least two classes of steroid compounds, plant derived ouabain (O), and several toad derived bufodienolides, most prominent being marinobufagenin (MBG). A synthetic pathway for MBG has been identified in mammalian placental tissue. Elevated maternal and fetal EDLF, O and MBG have been demonstrated in preeclampsia (PE), and inhibition of red cell membrane sodium, potassium ATPase (Na, K ATPase (NKA)) by EDLF is reversed by ADA fragments (ADA-FAB). Accordingly, maternal administration of a commercial ADA-antibody fragment (FAB) was tested in several anecdotal cases of PE, and two, small randomized, prospective, double-blind clinical trials. In the first randomized trial, ADA-FAB was administered post-partum, in the second antepartum. In the post-partum trial, ADA-FAB reduced use of antihypertensive drugs. In the second trial, there was no effect of ADA-FAB on blood pressure, but the fall in maternal creatinine clearance (CrCl) was prevented. In a secondary analysis using the pre-treatment maternal level of circulating Na, K ATPase (NKA) inhibitory activity (NKAI), ADA-FAB reduced the incidence of pulmonary edema and, unexpectedly, that of severe neonatal intraventricular hemorrhage (IVH). The fall in CrCl in patients given placebo was proportional to the circulating level of NKAI. The implications of these findings on the pathophysiology of the clinical manifestations PE are discussed, and a new model of the respective roles of placenta derived anti-angiogenic (AAG) factors (AAGFs) and EDLF is proposed.


1992 ◽  
Vol 33 (3) ◽  
pp. 185-186 ◽  
Author(s):  
Mark C. Maberry ◽  
Kenneth J. Trimmer ◽  
Roger E. Bawdon ◽  
Sorab Sobhi ◽  
Jody B. Dax ◽  
...  

2014 ◽  
Vol 6 ◽  
pp. OED.S17671 ◽  
Author(s):  
Kalina Andreeva ◽  
Meixia Zhang ◽  
Wei Fan ◽  
Xiaohong Li ◽  
Yinlu Chen ◽  
...  

Ischemia/reperfusion (IR) injury has been associated with several retinal pathologies, and a few genes/gene products have been linked to IR injury. However, the big picture of temporal changes, regarding the affected gene networks, pathways, and processes remains to be determined. The purpose of the present study was to investigate initial, intermediate, and later stages to characterize the etiology of IR injury in terms of the pathways affected over time. Analyses indicated that at the initial stage, 0-hour reperfusion following the ischemic period, the ischemia-associated genes were related to changes in metabolism. In contrast, at the 24-hour time point, the signature events in reperfusion injury include enhanced inflammatory and immune responses as well as cell death indicating that this would be a critical period for the development of any interventional therapeutic strategies. Genes in the signal transduction pathways, particularly transmitter receptors, are downregulated at this time. Activation of the complement system pathway clearly plays an important role in the later stages of reperfusion injury. Together, these results demonstrate that the etiology of injury related to IR is characterized by the appearance of specific patterns of gene expression at any given time point during retinal IR injury. These results indicate that evaluation of treatment strategies with respect to time is very critical.


2000 ◽  
pp. 683-687 ◽  
Author(s):  
K Kobayashi ◽  
T Kubota ◽  
T Aso ◽  
Y Hirata ◽  
T Imai ◽  
...  

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.


It has long been known that maternal circulating antibodies pass into the foetal blood in rabbits during the latter half of pregnancy. The allanto-chorionic placenta has been assumed to be the site of this transference, the number of tissues separating the two blood streams being reduced to a minimum in rabbits at these stages. It was shown in a recent paper that, at a stage before the establishment of the embryonic circulation, maternal circulating antibodies pass the bilaminar omphalopleur into the yolk-sac cavity. It is shown in this paper that in 24-day embryos antibodies pass from the maternal circulation by way of the uterine lumen and the yolk-sac splanchnopleur into the foetal vitelline circulation, and do not pass by way of the allanto-chorionic placenta. The method employed involved injection of immune rabbit serum either into the uterine lumen or the maternal blood and interruption of the foetal vitelline circulation of some of the embryos by ligaturing the yolk-sac stalk.


Author(s):  
Anahita Shaer ◽  
Negar Azarpira ◽  
Akbar Vahdati ◽  
Mohammad Karimi ◽  
Mehrdad Shariati

AbstractThis paper focuses on the development of renewable sources of isletreplacement tissue for the treatment of type I diabetes mellitus. Placental tissue-derived mesenchymal stem cells (MSCs) are a promising source for regenerative medicine due to their plasticity and easy availability. They have the potential to differentiate into insulin-producing cells. miR-375 is a micro RNA that is expressed in the pancreas and involved in islet development. Human placental decidua basalis MSCs (PDB-MSCs) were cultured from full-term human placenta. The immunophenotype of the isolated cells was checked for CD90, CD105, CD44, CD133 and CD34 markers. The MSCs (P3) were chemically transfected with hsa-miR-375. Total RNA was extracted 4 and 6 days after transfection. The expressions of insulin, NGN3, GLUT2, PAX4, PAX6, KIR6.2, NKX6.1, PDX1, and glucagon genes were evaluated using real-time qPCR. On day 6, we tested the potency of the clusters in response to the high glucose challenge and assessed the presence of insulin and NGN3 proteins via immunocytochemistry. Flow cytometry analysis confirmed that more than 90% of the cells were positive for CD90, CD105 and CD44 and negative for CD133 and CD34. Morphological changes were followed from day 2. Cell clusters formed during day 6. Insulin-producing clusters showed a deep red color with DTZ. The expression of pancreatic-specific transcription factors increased remarkably during the four days after transfection and significantly increased on day 7. The clusters were positive for insulin and NGN3 proteins, and C-peptide and insulin secretion increased in response to changes in the glucose concentration (2.8 mM and 16.7 mM). In conclusion, the MSCs could be programmed into functional insulin-producing cells by transfection of miR-375.


1992 ◽  
Vol 134 (2) ◽  
pp. 313-317 ◽  
Author(s):  
M. R. Johnson ◽  
A. Abbas ◽  
K. H. Nicolaides ◽  
S. L. Lightman

ABSTRACT Relaxin was measured in maternal blood and amniotic fluid samples at 9–40 weeks and in fetal blood samples at 19–41 weeks of pregnancy. In amniotic fluid, concentrations of relaxin rose from 58 ng/1 (geometric mean) at 10 weeks to 142 ng/l at 14 weeks and declined subsequently to 55 ng/l at 22 weeks. In maternal blood, mean relaxin concentrations were ten times greater than in amniotic fluid, and concentrations decreased with gestation. Since there was no significant association between the relaxin concentrations in the two compartments, relaxin in the amniotic fluid may be derived from the decidualized endometrium rather than the maternal circulation, alternatively its metabolism may be different in the two compartments. The absence of detectable concentrations of relaxin in any of the fetal blood samples demonstrates that there is no significant placental transfer or fetal synthesis of this peptide. Journal of Endocrinology (1992) 134, 313–317


2014 ◽  
Vol 155 (47) ◽  
pp. 1860-1866 ◽  
Author(s):  
Bálint Alasztics ◽  
Nóra Gullai ◽  
Attila Molvarec ◽  
János Rigó Jr.

Preeclampsia is one of the most common and most serious complications of pregnancy and the management of this condition still challenges obstetricians. Despite intensive research the etiology of preeclampsia still remains unclear. At the beginning of the 2000s preeclampsia-related research was directed towards factors that influence angiogenesis. Most studies have been carried out on the placental growth factor and soluble fms-like tyrosine kinase-1. Most publications confirm the increased concentrations of antiangiogenic factors and decreased concentrations of proangiogenic factors in maternal blood samples in preeclampsia even before the onset of clinical symptoms. According to our current knowledge antiangiogenic proteins are responsible for the endothelial dysfunction in the symptomatic stage of the disease. Placental growth factor and soluble fms-like tyrosine kinase-1 may have important roles in the prediction and treatment of the disease. The point of care detection of placental growth factor and soluble fms-like tyrosine kinase-1 may be used to predict preeclampsia. Rapid tests are available to determine the serum levels of the two proteins. Removal of soluble fms-like tyrosine kinase-1 from maternal circulation is a potential treatment option for early onset preeclampsia. Orv. Hetil., 2014, 155(47), 1860–1866.


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