Coagulation signaling from amniotic fluid to fetal skin.
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ABSTRACT:
SUBMITTER: Hu Y
PROVIDER: S-EPMC9647714 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
Coagulation signaling from amniotic fluid to fetal skin.
Hu Yong Y Scharrer Anke A Hau Chi C Ay Cihan C Berckmans René J RJ Ruf Wolfram W Nieuwland Rienk R Thaler Johannes J
Blood advances 20221001 19
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Project description:BackgroundResearch into cell-free fetal (cff) nucleic acids has primarily focused on maternal plasma; however, cff DNA and RNA are also detectable in other body fluids such as amniotic fluid (AF). In AF, cff DNA is present in much greater concentrations than in maternal plasma and represents a pure fetal sample uncontaminated by maternal- and trophoblast-derived nucleic acids. The aim of this review was to summarize the current knowledge on cff nucleic acids in AF and to outline future research directions.MethodsMEDLINE and PREMEDLINE were searched up to August 2010 for original investigations of cell-free RNA or DNA in AF. Sixteen studies were included in the review.ResultsAF cff DNA represents a physiologically separate pool from cff DNA in maternal plasma. The placenta is not a major source of nucleic acids in AF. It is feasible to isolate cff nucleic acids from small volumes of discarded AF supernatant in sufficient quality and quantity to perform microarray studies and downstream applications such as pathway analysis. This 'discovery-driven approach' has resulted in new information on the pathogenesis of Down syndrome and polyhydramnios. There is otherwise a paucity of information relating to the basic biology and clinical applications of cff nucleic acids in AF.ConclusionsAF supernatant is a valuable and widely available but under-utilized biological resource. Further studies of cff nucleic acids in AF may lead to new insights into human fetal development and ultimately new approaches to antenatal treatment of human disease.
| S-EPMC3072021 | biostudies-literature
Project description:Amniotic fluid is essential for fetus wellbeing and is used to monitor pregnancy and predict fetal outcomes. Sex affects health and medicine from the beginning of life, but knowledge of its influence on cell-depleted amniotic fluid (AF) and amniotic fluid cells (AFCs) is still neglected. We evaluated sex-related differences in AF and in AFCs to extend personalized medicine to prenatal life. AFCs and AF were obtained from healthy Caucasian pregnant women who underwent amniocentesis at the 16th-18th week of gestation for advanced maternal age. In the AF, inflammation biomarkers (TNFα, IL6, IL8, and IL4), malondialdehyde, nitrites, amino acids, and acylcarnitines were measured. Estrogen receptors and cell fate (autophagy, apoptosis, senescence) were measured in AFCs. TNFα, IL8, and IL4 were higher in female AF, whereas IL6, nitrites, and MDA were similar. Valine was higher in male AF, whereas several acylcarnitines were sexually different, suggesting a mitochondrial involvement in establishing sex differences. Female AFCs displayed higher expression of ERα protein and a higher ERα/ERβ ratio. The ratio of LC3II/I, an index of autophagy, was higher in female AFCs, while LC3 gene was similar in both sexes. No significant sex differences were found in the expression of the lysosomal protein LAMP1, while p62 was higher in male AFCs. LAMP1 gene was upregulated in male AFCs, while p62 gene was upregulated in female ones. Finally, caspase 9 activity and senescence linked to telomeres were higher in female AFCs, while caspase 3 and β-galactosidase activities were similar. This study supports the idea that sex differences start very early in prenatal life and influence specific parameters, suggesting that it may be relevant to appreciate sex differences to cover knowledge gaps. This might lead to improving the diagnosis of risk prediction for pregnancy complications and achieving a more satisfactory monitoring of fetus health, even preventing future diseases in adulthood.
| S-EPMC10604128 | biostudies-literature
Project description:The fetal intestinal mucosa is characterized by elevated Toll-like receptor 4 (TLR4) expression, which can lead to the development of necrotizing enterocolitis (NEC)--a devastating inflammatory disease of the premature intestine--upon exposure to microbes. To define endogenous strategies that could reduce TLR4 signaling, we hypothesized that amniotic fluid can inhibit TLR4 signaling within the fetal intestine and attenuate experimental NEC, and we sought to determine the mechanisms involved. We show here that microinjection of amniotic fluid into the fetal (embryonic day 18.5) gastrointestinal tract reduced LPS-mediated signaling within the fetal intestinal mucosa. Amniotic fluid is abundant in EGF, which we show is required for its inhibitory effects on TLR4 signaling via peroxisome proliferator-activated receptor, because inhibition of EGF receptor (EGFR) with cetuximab or EGF-depleted amniotic fluid blocked the inhibitory effects of amniotic fluid on TLR4, whereas amniotic fluid did not prevent TLR4 signaling in EGFR- or peroxisome proliferator-activated receptor ?-deficient enterocytes or in mice deficient in intestinal epithelial EGFR, and purified EGF attenuated the exaggerated intestinal mucosal TLR4 signaling in wild-type mice. Moreover, amniotic fluid-mediated TLR4 inhibition reduced the severity of NEC in mice through EGFR activation. Strikingly, NEC development in both mice and humans was associated with reduced EGFR expression that was restored upon the administration of amniotic fluid in mice or recovery from NEC in humans, suggesting that a lack of amniotic fluid-mediated EGFR signaling could predispose to NEC. These findings may explain the unique susceptibility of premature infants to the development of NEC and offer therapeutic approaches to this devastating disease.
| S-EPMC3396489 | biostudies-literature
Project description:Myelomeningocele (MMC) is a congenital disease without genetic abnormalities. Neurological symptoms are irreversibly impaired after birth, and no effective treatment has been reported to date. Only surgical repairs have been reported so far. In this study, we performed antenatal treatment of MMC with an artificial skin using induced pluripotent stem cells (iPSCs) generated from a patient with Down syndrome (AF-T21-iPSCs) and twin-twin transfusion syndrome (AF-TTTS-iPSCs) to a rat model. We manufactured three-dimensional skin with epidermis generated from keratinocytes derived from AF-T21-iPSCs and AF-TTTS-iPSCs and dermis of human fibroblasts and collagen type I. For generation of epidermis, we developed a protocol using Y-27632 and epidermal growth factor. The artificial skin was successfully covered over MMC defect sites during pregnancy, implying a possible antenatal surgical treatment with iPSC technology.
| S-EPMC5470234 | biostudies-literature
Project description:BackgroundFetal growth restriction (FGR) is typically characterised as the fetus' inability to reach its inherent growth potential. A growing body of evidence points to the important role of the maternal gut microbiota in FGR development. However, comprehensive research on changes in maternal-fetal gut and intrauterine microbiota related to FGR is lacking.MethodsIn this case-control study, we sequenced bacterial 16S rRNA from 35 maternal faecal, 35 meconium, and 31 amniotic fluid samples collected from 19 pregnant women diagnosed with FGR and 16 healthy controls. We identified putative bacterial taxonomic and functional characteristics associated with FGR by comparing these to control samples.ResultsWe identified 34 differential operational taxonomic units (OTUs) in amniotic fluid, seven differential OTUs in maternal faecal matter, and two differential OTUs in meconium. Compared to controls, FGR subjects exhibited enriched bacterial OTUs of the genus Bacteroides in the maternal gut. They also had depleted OTUs of the order Enterobacterales and genus Pseudomonas in the amniotic fluid and genus Stenotrophomonas in the fetal gut. These altered bacterial OTUs showed a significant correlation with neonatal weight and fetal ultrasonographic indexes. Additionally, we identified differential microbial functional pathways related to glycan and lipid metabolism in the maternal gut. We developed diagnostic biomarkers for FGR based on the maternal-fetal gut and amniotic fluid microbiota.ConclusionsThis study offers a comprehensive overview of the shifts in microbial composition and functional pathways in the maternal-fetal gut and amniotic fluid microbiota related to FGR, and present novel insights into the development and screening of FGR. However, the assessment of contamination's impact on meconium and amniotic fluid remains inconclusive, necessitating further rigorous experimentation to address this scientific inquiry in future studies.
| S-EPMC11546114 | biostudies-literature
Project description:In mammals, sex development is genetically and hormonally regulated. The process starts with the establishment of chromosomal structures (XY or XX), followed by the expression of sex-dependent genes. In order to elucidate the differential protein profiles between male and female amniocytes, a proteomic approach has been performed in this study. Here, we utilized a proteomics-based approach including 2D-DIGE and MALDI-TOF MS analysis to obtain differentially expressed proteins between male and female amniocytes. After resolving protein samples with 2D-DIGE technique, 45 proteins corresponding to 28 unique proteins were differentially expressed between male and female amninocytes from three independent batches of amniotic fluid. Of all of these unique identified spots, five of them (annexin A1, cathepsin D, cytoskeletal 19, protein disulfide-isomerase, and vimentin) exhibited more than 1.5-fold upregulation or downregulation in at least two independent experiments. Importantly, the identified proteins involved in protein degradation and protein folding display upregulated in male amniocytes, implying the differential regulations of protein degradation and protein folding during sex development. In conclusion, the identified differentially expressed proteins may be employed as potential signatures for the sex development. Moreover, the established proteomic platform might further utilize to discover the potential biomarkers for the prenatal genetic disorders in fetus.
| S-EPMC3545359 | biostudies-literature
Project description:Tissue hypoxia is the major stimulus of erythropoietin (EPO) synthesis in fetuses and adults. Since EPO does not cross the placenta and is not stored, fetal plasma and amniotic fluid levels indicate EPO synthesis and elimination. Acutely, the rate and magnitude of the increase in plasma EPO levels correlate with the intensity of hypoxia. Amniotic fluid EPO levels correlate with cord plasma levels in normal and abnormal pregnancies, with fetal plasma EPO levels in humans averaging 2.6 times higher than the corresponding amniotic fluid EPO levels. Recent experimental and clinical studies demonstrate that EPO has neuroprotective effects related to its anti-apoptotic and vascular growth-promoting properties. Although under basal conditions the fetal kidneys are the main site of EPO production, during hypoxia recent experimental data indicate an important role of the placenta. Amniotic fluid EPO levels have been shown to increase exponentially during fetal hypoxia in preeclamptic, diabetic and Rh-immunized pregnancies, to correlate inversely with cord blood pH, pO(2) and base excess and to predict neonatal morbidities and NICU admission. As an indicator of chronic intrauterine hypoxia, fetal EPO measurements have increased our knowledge about the pathogenesis and importance of intrauterine growth restriction, macrosomia, diabetic pregnancy, prolonged pregnancy, meconium staining, fetal hemorrhage, fetal anemia, maternal smoking and alcohol consumption, abnormal fetal heart rate and abnormal Doppler flow patterns. While the clinical utility of fetal amniotic fluid and plasma EPO measurements in the management of high-risk pregnancies and their offspring is promising, adequately powered clinical trials are urgently needed.
| S-EPMC2863306 | biostudies-other
Project description:IntroductionAt the maternal-fetal interface in pregnancy, stress during pregnancy can lead to an increased vulnerability to later psychopathology of the fetus. Potential mediators of this association have scarcely been studied and may include early alterations of fetal brain-derived neurotrophic factor (BDNF). Amniotic fluid is of particular interest for effects on fetal endocrine alterations, as the assessment in amniotic fluid allows for measurements over a time integral. This study hypothesized that maternal psychometrics, socioeconomic status and glucocorticoids are related to BDNF levels in amniotic fluid at birth. The association of fetal BDNF with newborn anthropometrics was tested.MethodsWomen near term who underwent elective cesarean section and their newborns were investigated (n = 37). Maternal psychometrics, socioeconomic status and glucocorticoids (the sum of cortisol and cortisone) in amniotic fluid at birth were analyzed for an association with fetal BDNF in amniotic fluid at birth. Newborn anthropometrics were assessed by length, weight, head circumference and gestational age at birth.ResultsIn bivariate analysis, maternal psychometrics and socioeconomic status were not related to fetal BDNF in amniotic fluid at birth. The sum of cortisol and cortisone related to increased fetal BDNF in amniotic fluid at birth (r = 0.745, p < 0.001). BDNF in amniotic fluid was associated negatively with fetal birth weight per gestational age (r = -0.519, p < 0.001), length per gestational age (r = -0.374, p = 0.023), head circumference per gestational age (r = -0.508, p = 0.001), but not with gestational age at birth. In multiple regression analysis, the sum of cortisol and cortisone (p < 0.001) and birth weight per gestational age (p = 0.012) related to higher fetal BDNF levels in amniotic fluid at birth (R2 = 0.740, p < 0.001) when controlling for fetal sex and maternal age. Head circumference per gestational age predicted fetal BDNF with borderline significance (p = 0.058) when controlling for confounders.ConclusionGlucocorticoids in amniotic fluid were positively associated with high fetal BDNF at birth, which may be an adaptive fetal response. Maternal psychological variables and socioeconomic status did not link to fetal BDNF. Birth weight and head circumference per gestational age were inversely associated with fetal BDNF at birth, which may represent a compensatory upregulation of BDNF in fetuses with low anthropometrics. Longitudinal studies are needed to assess the role of stress during pregnancy on later offspring development. The analysis of additional fetal growth factors and inflammation upon maternal stress in further biomaterials such as the placenta is warranted, to understand mechanistic alterations of how maternal stress links to fetal development and an increased vulnerability for psychopathology.
| S-EPMC11294724 | biostudies-literature
Project description:Accurate estimate of fetal maturity could provide individualized guidance for delivery of complicated pregnancies. However, current methods are invasive, have low accuracy, and are limited to fetal lung maturation. To identify diagnostic gestational biomarkers, we performed transcriptomic profiling of lung and brain, as well as cell-free RNA from amniotic fluid of preterm and term rhesus macaque fetuses. These data identify potentially new and prior-associated gestational age differences in distinct lung and neuronal cell populations when compared with existing single-cell and bulk RNA-Seq data. Comparative analyses found hundreds of genes coincidently induced in lung and amniotic fluid, along with dozens in brain and amniotic fluid. These data enable creation of computational models that accurately predict lung compliance from amniotic fluid and lung transcriptome of preterm fetuses treated with antenatal corticosteroids. Importantly, antenatal steroids induced off-target gene expression changes in the brain, impinging upon synaptic transmission and neuronal and glial maturation, as this could have long-term consequences on brain development. Cell-free RNA in amniotic fluid may provide a substrate of global fetal maturation markers for personalized management of at-risk pregnancies.
| S-EPMC9675452 | biostudies-literature
Project description:Procoagulant activity in amniotic fluid (AF) is positively correlated with phosphatidylserine (PS) and tissue factor (TF)-expressing(+) extracellular vesicles (EVs). However, it is unknown if pathological fetal conditions may affect the composition, phenotype, and procoagulant potency of EVs in AF. We sought to evaluate EV-dependent procoagulant activity in AF from pregnant people with fetuses with or without diagnosed chromosomal mutations. AF samples were collected by transabdominal amniocentesis and assessed for common karyotype defects (total n = 11, 7 healthy and 4 abnormal karyotypes). The procoagulant activity of AF was tested using a fibrin generation assay with normal pooled plasma and plasmas deficient in factors XII, XI, IX, X, V, and VII. EV number and phenotype were determined by flow cytometry with anti-CD24 and anti-TF antibodies. We report that factor-VII-, X-, or V-deficient plasmas did not form fibrin clots in the presence of AF. Clotting time was significantly attenuated in AF samples with chromosomal mutations. In addition, CD24+, TF+, and CD24+ TF+ EV counts were significantly lower in this group. Finally, we found a significant correlation between EV counts and the clotting time induced by AF. In conclusion, we show that AF samples with chromosomal mutations had fewer fetal-derived CD24-bearing and TF-bearing EVs, which resulted in diminished procoagulant potency. This suggests that fetal-derived EVs are the predominant source of procoagulant activity in AF.
| S-EPMC9221817 | biostudies-literature