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International Journal of Molecular... Jan 2022Since the first evidence that stem cells can provide pro-resolving effects via paracrine secretion of soluble factors, growing interest has been addressed to define the... (Review)
Review
Since the first evidence that stem cells can provide pro-resolving effects via paracrine secretion of soluble factors, growing interest has been addressed to define the most ideal cell source for clinical translation. Leftover or clinical waste samples of human amniotic fluid obtained following prenatal screening, clinical intervention, or during scheduled caesarean section (C-section) delivery at term have been recently considered an appealing source of mesenchymal progenitors with peculiar regenerative capacity. Human amniotic fluid stem cells (hAFSC) have been demonstrated to support tissue recovery in several preclinical models of disease by exerting paracrine proliferative, anti-inflammatory and regenerative influence. Small extracellular vesicles (EVs) concentrated from the hAFSC secretome (the total soluble trophic factors secreted in the cell-conditioned medium, hAFSC-CM) recapitulate most of the beneficial cell effects. Independent studies in preclinical models of either adult disorders or severe diseases in newborns have suggested a regenerative role of hAFSC-EVs. EVs can be eventually concentrated from amniotic fluid (hAF) to offer useful prenatal information, as recently suggested. In this review, we focus on the most significant aspects of EVs obtained from either hAFSC and hAF and consider the current challenges for their clinical translation, including isolation, characterization and quantification methods.
Topics: Amniotic Fluid; Extracellular Vesicles; Humans; Precision Medicine; Stem Cells
PubMed: 35054775
DOI: 10.3390/ijms23020590 -
Organogenesis 2012
Topics: Amniotic Fluid; Animals; Cells, Cultured; Guided Tissue Regeneration; Humans; Stem Cell Research; Stem Cell Transplantation; Stem Cells
PubMed: 23187723
DOI: 10.4161/org.23023 -
BMC Medical Genomics Oct 2015Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for...
BACKGROUND
Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation.
METHODS
We isolated AF RNA from 16 women at different time points in pregnancy: 4 from 18 to 24 weeks, 6 from 34 to 36 weeks, and 6 from 39 to 40 weeks. RNA-sequencing was performed on cell-free RNA. Gene expression and splicing analyses were performed in conjunction with cell-type and pathway predictions.
RESULTS
Sample-level analysis at different time points in pregnancy demonstrated a strong correlation with cell types found in the intrauterine environment and fetal respiratory, digestive and external barrier tissues of the fetus, using high-confidence cellular molecular markers. While some RNAs and splice variants were present throughout pregnancy, many transcripts were uniquely expressed at different time points in pregnancy and associated with distinct neonatal co-morbidities (respiratory distress and gavage feeding), indicating fetal immaturity.
CONCLUSION
The AF transcriptome exhibits unique cell/organ-selective expression patterns at different time points in pregnancy that can potentially identify fetal organ maturity and predict neonatal morbidity. Developing novel biomarkers indicative of the maturation of multiple organ systems can improve upon our current methods of fetal maturity testing which focus solely on the lung, and will better inform obstetrical decisions regarding delivery timing.
Topics: Amniotic Fluid; Comorbidity; Female; Fetal Organ Maturity; Gene Expression Profiling; Humans; Infant, Premature; Male; Pregnancy; Sequence Analysis, RNA; Systems Biology; Term Birth
PubMed: 26493725
DOI: 10.1186/s12920-015-0138-5 -
Scientific Reports Feb 2023The intra-uterine components of labor, namely, myometrial contractility, cervical ripening, and decidua/membrane activation, have been extensively characterized and...
The intra-uterine components of labor, namely, myometrial contractility, cervical ripening, and decidua/membrane activation, have been extensively characterized and involve a local pro-inflammatory milieu of cellular and soluble immune mediators. Targeted profiling has demonstrated that such processes extend to the intra-amniotic space, yet unbiased analyses of the proteome of human amniotic fluid during labor are lacking. Herein, we utilized an aptamer-based platform to characterize 1,310 amniotic fluid proteins and found that the proteome undergoes substantial changes with term labor (251 proteins with differential abundance, q < 0.1, and fold change > 1.25). Proteins with increased abundance in labor are enriched for immune and inflammatory processes, consistent with prior reports of labor-associated changes in the intra-uterine space. By integrating the amniotic fluid proteome with previously generated placental-derived single-cell RNA-seq data, we demonstrated the labor-driven upregulation of signatures corresponding to stromal-3 and decidual cells. We also determined that changes in amniotic fluid protein abundance are reflected in the maternal plasma proteome. Collectively, these findings provide novel insights into the amniotic fluid proteome in term labor and support its potential use as a source of biomarkers to distinguish between true and false labor by using maternal blood samples.
Topics: Pregnancy; Female; Humans; Amniotic Fluid; Proteome; Obstetric Labor, Premature; Placenta; Biomarkers
PubMed: 36823217
DOI: 10.1038/s41598-023-28157-3 -
Toxins Jun 2021Mycotoxin exposure assessments through biomonitoring studies, based on the analysis of amniotic fluid, provides useful information about potential exposure of mothers...
Mycotoxin exposure assessments through biomonitoring studies, based on the analysis of amniotic fluid, provides useful information about potential exposure of mothers and fetuses to ubiquitous toxic metabolites that are routinely found in food and the environment. In this study, amniotic fluid samples (n = 86) were collected via abdominal amniocentesis at 15-22 weeks of gestation from pregnant women with a high risk of chromosomal anomalies or genetic fetal defects detected during 1st trimester prenatal screening. These samples were analyzed for the presence of the most typical , and mycotoxins, with a focus on aflatoxins, ochratoxins and trichothecenes, using the LC-FLD/DAD method. The results showed that the toxin was present in over 75% of all the tested samples and in 73% of amniotic fluid samples from fetuses with genetic defects. The most frequently identified toxins were nivalenol (33.7%) ranging from
amniotic fluid is useful for the estimation of overall risk characterization with an attempt to link the occurrence of fetal abnormalities with exposure to mycotoxins in utero. Topics: Amniotic Fluid; Biological Monitoring; Congenital Abnormalities; Female; Fetus; Humans; Mycotoxins; Pregnancy; Pregnancy Trimester, Second
PubMed: 34207874
DOI: 10.3390/toxins13060409 -
Reproductive Toxicology (Elmsford, N.Y.) Apr 2022Exposure to trichloroethylene (TCE), an industrial solvent, is associated with several adverse pregnancy outcomes in humans and decreased fetal weight in rats. However,...
Exposure to trichloroethylene (TCE), an industrial solvent, is associated with several adverse pregnancy outcomes in humans and decreased fetal weight in rats. However, effects of TCE on energy metabolites in amniotic fluid, which have associations with pregnancy outcomes, has not been published previously. In the current exploratory study, timed-pregnant Wistar rats were exposed to 480 mg TCE/kg/day via vanilla wafer or to vehicle (wafer) alone from gestational day (GD) 6-16. Amniotic fluid collected on GD 16 was analyzed for metabolites important in energy metabolism using short chain fatty acid and tricarboxylic acid plus platforms (N = 4 samples/sex/treatment). TCE decreased concentrations of the following metabolites in amniotic fluid for both fetal sexes: 6-phosphogluconate, guanosine diphosphate, adenosine diphosphate, adenosine triphosphate, and flavin adenine dinucleotide. TCE decreased fructose 1,6-bisphosphate and guanosine triphosphate concentrations in amniotic fluid of male but not female fetuses. Moreover, TCE decreased uridine diphosphate-D-glucuronate concentrations, and increased arginine and phosphocreatine concentrations, in amniotic fluid of female fetuses only. No metabolites were increased in amniotic fluid of male fetuses. Pathway analysis suggested that TCE altered folate biosynthesis and pentose phosphate pathway in both sexes. Using metabolite ratios to investigate changes within specific pathways, some ratio alterations, including those in arginine metabolism and phenylalanine metabolism, were detected in females only. Ratio analysis also suggested enzymes, including gluconokinase, as potential TCE targets. Together, results from this exploratory study suggest that TCE differentially modified energy metabolites in amniotic fluid based on sex. These findings may inform future studies of TCE reproductive toxicity.
Topics: Amniotic Fluid; Animals; Female; Male; Pregnancy; Pregnancy Outcome; Rats; Rats, Wistar; Solvents; Trichloroethylene
PubMed: 35301063
DOI: 10.1016/j.reprotox.2022.03.004 -
Medical Image Analysis Apr 2021The estimation of antenatal amniotic fluid (AF) volume (AFV) is important as it offers crucial information about fetal development, fetal well-being, and perinatal...
The estimation of antenatal amniotic fluid (AF) volume (AFV) is important as it offers crucial information about fetal development, fetal well-being, and perinatal prognosis. However, AFV measurement is cumbersome and patient specific. Moreover, it is heavily sonographer-dependent, with measurement accuracy varying greatly depending on the sonographer's experience. Therefore, the development of accurate, robust, and adoptable methods to evaluate AFV is highly desirable. In this regard, automation is expected to reduce user-based variability and workload of sonographers. However, automating AFV measurement is very challenging, because accurate detection of AF pockets is difficult owing to various confusing factors, such as reverberation artifact, AF mimicking region and floating matter. Furthermore, AF pocket exhibits an unspecified variety of shapes and sizes, and ultrasound images often show missing or incomplete structural boundaries. To overcome the abovementioned difficulties, we develop a hierarchical deep-learning-based method, which consider clinicians' anatomical-knowledge-based approaches. The key step is the segmentation of the AF pocket using our proposed deep learning network, AF-net. AF-net is a variation of U-net combined with three complementary concepts - atrous convolution, multi-scale side-input layer, and side-output layer. The experimental results demonstrate that the proposed method provides a measurement of the amniotic fluid index (AFI) that is as robust and precise as the results from clinicians. The proposed method achieved a Dice similarity of 0.877±0.086 for AF segmentation and achieved a mean absolute error of 2.666±2.986 and mean relative error of 0.018±0.023 for AFI value. To the best of our knowledge, our method, for the first time, provides an automated measurement of AFI.
Topics: Amniotic Fluid; Deep Learning; Female; Humans; Pregnancy; Ultrasonography
PubMed: 33515982
DOI: 10.1016/j.media.2020.101951 -
Frontiers in Immunology 2021Intra-amniotic infection and inflammation (IAI) affect fetal development and are highly associated with preterm labor and premature rupture of membranes, which often... (Review)
Review
Intra-amniotic infection and inflammation (IAI) affect fetal development and are highly associated with preterm labor and premature rupture of membranes, which often lead to adverse neonatal outcomes. Human amniotic membrane (hAM), the inner part of the amnio-chorionic membrane, protects the embryo/fetus from environmental dangers, including microbial infection. However, weakened amnio-chorionic membrane may be breached or pathogens may enter through a different route, leading to IAI. The hAM and human amniotic fluid (hAF) respond by activation of all components of the innate immune system. This includes changes in 1) hAM structure, 2) presence of immune cells, 3) pattern recognition receptors, 4) cytokines, 5) antimicrobial peptides, 6) lipid derivatives, and 7) complement system. Herein we provide a comprehensive and integrative review of the current understanding of the innate immune response in the hAM and hAF, which will aid in design of novel studies that may lead to breakthroughs in how we perceive the IAI.
Topics: Amnion; Amniotic Fluid; Animals; Bacteria; Bacterial Infections; Chorioamnionitis; Female; Host-Pathogen Interactions; Humans; Immunity, Innate; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Signal Transduction
PubMed: 34745106
DOI: 10.3389/fimmu.2021.735324 -
Journal of Perinatal Medicine Feb 2020Background Intra-amniotic inflammation, which is associated with adverse pregnancy outcomes, can occur in the presence or absence of detectable microorganisms, and...
Background Intra-amniotic inflammation, which is associated with adverse pregnancy outcomes, can occur in the presence or absence of detectable microorganisms, and involves activation of the inflammasome. Intra-amniotic inflammasome activation has been reported in clinical chorioamnionitis at term and preterm labor with intact membranes, but it has not yet been investigated in women with preterm prelabor rupture of membranes (preterm PROM) in the presence/absence of detectable microorganisms. The aim of this study was to determine whether, among women with preterm PROM, there is an association between detectable microorganisms in amniotic fluid and intra-amniotic inflammation, and whether intra-amniotic inflammasome activation correlates with microbial burden. Methods Amniotic fluids from 59 cases of preterm PROM were examined for the presence/absence of microorganisms through culture and 16S ribosomal RNA (rRNA) gene quantitative real-time polymerase chain reaction (qPCR), and concentrations of interleukin-6 (IL-6) and ASC [apoptosis-associated spec-like protein containing a caspase recruitment domain (CARD)], an indicator of inflammasome activation, were determined. Results qPCR identified more microbe-positive amniotic fluids than culture. Greater than 50% of patients with a negative culture and high IL-6 concentration in amniotic fluid yielded a positive qPCR signal. ASC concentrations were greatest in patients with high qPCR signals and elevated IL-6 concentrations in amniotic fluid (i.e. intra-amniotic infection). ASC concentrations tended to increase in patients without detectable microorganisms but yet with elevated IL-6 concentrations (i.e. sterile intra-amniotic inflammation) compared to those without intra-amniotic inflammation. Conclusion qPCR is a valuable complement to microbiological culture for the detection of microorganisms in the amniotic cavity in women with preterm PROM, and microbial burden is associated with the severity of intra-amniotic inflammatory response, including inflammasome activation.
Topics: Adult; Amniotic Fluid; CARD Signaling Adaptor Proteins; Cross-Sectional Studies; Female; Fetal Membranes, Premature Rupture; Humans; Inflammasomes; Pregnancy; RNA, Ribosomal, 16S; Real-Time Polymerase Chain Reaction; Retrospective Studies; Young Adult
PubMed: 31927525
DOI: 10.1515/jpm-2019-0398 -
Biomedicine & Pharmacotherapy =... Oct 2022Acetaminophen is among the most widely used analgesics; however, the proportion and mechanism of transplacental transfer of unbound acetaminophen with actual...
Acetaminophen is among the most widely used analgesics; however, the proportion and mechanism of transplacental transfer of unbound acetaminophen with actual pharmacological activity remain unknown. Our hypothesis is that acetaminophen gradually penetrates the blood-placenta barrier to reach the fetus. A multiple microdialysis coupled to liquid chromatography with photodiode array detection method was developed to monitor acetaminophen levels in the maternal blood, placenta, fetus, and amniotic fluid of a pregnant rat and investigate this hypothesis. The pharmacokinetic data indicates that acetaminophen exhibits a nonlinear behavior in the maternal blood within the dosage regimen of 100 and 300 mg/kg. In addition, acetaminophen penetrates the placenta, fetus, and amniotic fluid during treatment. The transplacental transfer ratio represented by the area under the concentration curve (AUC) ratio for the conceptus (the collective term for the fetus, placenta, and amniotic fluid) and maternal blood (AUC/AUC) was approximately 11-23 % after acetaminophen (100 and 300 mg/kg) administration. However, the transporter of multidrug resistance-associated protein (MRP) inhibitor MK-571 did not significantly change the transplacental transfer ratio. This basic study provides constructive information for the clinical application of acetaminophen in pregnant women.
Topics: Acetaminophen; Amniotic Fluid; Animals; Chromatography, Liquid; Female; Fetus; Humans; Maternal-Fetal Exchange; Placenta; Pregnancy; Rats
PubMed: 36058146
DOI: 10.1016/j.biopha.2022.113613