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Gene Jun 2024This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473...
This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VI), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VI, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.
PubMed: 38942180
DOI: 10.1016/j.gene.2024.148727 -
European Journal of Dentistry Jun 2024The current research aimed to evaluate the histopathological pulpal alterations in dogs' teeth following direct pulp capping using either mineral trioxide aggregate...
OBJECTIVE
The current research aimed to evaluate the histopathological pulpal alterations in dogs' teeth following direct pulp capping using either mineral trioxide aggregate (MTA) or human placenta extract (HPE).
MATERIALS AND METHODS
Forty-eight incisors with mature apices from four dogs were involved. The teeth were randomly allocated to three groups ( = 16) based on the material utilized for direct pulp capping: MTA, HPE, and Teflon as the negative control group. All involved teeth were capped and restored at the same session. Each group was subsequently divided into two subgroups ( = 8) based on the post treatment evaluation period: 2 and 4 weeks. The histopathologic changes in each specimen's pulp tissues, including pulp inflammation, hyperemia, necrosis, and dentin bridge development, were assessed. Then, all the data were statistically analyzed using chi-square, -test, and one-way analysis of variance ( < 0.05).
RESULTS
At 2 weeks, chronic inflammation was observed in 100% of MTA and 50% of HPE subgroups with a significant difference between them whereas the remaining 50% exhibited no inflammation. In contrast to Teflon that showed acute inflammation, remission of inflammation was time-dependent at both MTA and HPE subgroups as there was a substantial difference between the 2- and 4-weeks evaluation periods within the same group. However, throughout the initially observed 2 weeks, all subgroups exhibited essentially no complete calcified bridge; at 4 weeks, all MTA and HPE subgroups developed dentin bridge formation, with a significant difference between them regarding its thickness.
CONCLUSION
HPE is a promising pulp-capping material inducing less intense chronic inflammation accompanied with thicker dentine bridge formation in comparison to MTA.
PubMed: 38942055
DOI: 10.1055/s-0044-1786841 -
Reproductive Biology Jun 2024Mesenchymal cells within theplacental villi play a crucial role in shaping the morphology of branching structures and driving the development of blood vessels. However,...
Mesenchymal cells within theplacental villi play a crucial role in shaping the morphology of branching structures and driving the development of blood vessels. However, the markers and functions of placental villous pericytes (PVPs) as distinct subgroups of placental villous mesenchymal cells, remain unclear. Therefore, in this study, the markers and functions of PVPs were investigated. Single-cell sequencing data from the first-trimester placental villi was obtained and the Seurat tool was used to identify PVP markers. Gene Ontology (GO) analysis of specific genes was performed using the DAVID database. The Cellchat tool was employed to investigate the interaction signals between the PVPs and other cells. Expression of the PVP markers was confirmed using immunofluorescence. Presence of extracellular vesicles in the placental villous mesenchyme and PVPs was examined by transmission electron microscopy. Our findings revealed that renin (REN) and amphiregulin (AREG)-positive fibroblasts in the placental villi specifically expressed several classic pericyte markers. In the first trimester, certain conserved functions of pericytes were observed and they displayed tissue-specific functions such as in the integrin-mediated signaling pathway and extracellular exosomes. Moreover, the placental villous mesenchyme was found to be rich in extracellular vesicles. AREG is specifically transcribed in the first trimester PVPs, however, its protein was located in syncytiotrophoblasts. These insights contribute to a comprehensive understanding of early placental development and offer new therapeutic targets for placenta-derived pregnancy complications.
PubMed: 38941941
DOI: 10.1016/j.repbio.2024.100919 -
Journal of Reproductive Immunology Jun 2024Chronic Intervillositis of Unknown Etiology (CIUE) is a rare idiopathic inflammatory disorder of the placenta. The evidence suggests an increased risk for poor... (Review)
Review
Chronic Intervillositis of Unknown Etiology (CIUE) is a rare idiopathic inflammatory disorder of the placenta. The evidence suggests an increased risk for poor obstetrical outcomes and a risk of recurrence as high as 100 %. This meta-analysis examined CIUE prevalence, recurrence, association with autoimmune disorders, reproductive outcomes, pregnancy complications, and the benefits of medical treatments. A systematic review, following PRISMA guidelines, involved a thorough search across multiple databases including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Evidence Based Medical Reviews, and Scopus. Out of 590 initially identified studies, 19 studies were included for both qualitative synthesis and meta-analysis after full-text review. Risk of bias was assessed using appropriate tools: The Risk Of Bias In Non-randomized Studies of Interventions tool was applied to twelve studies, while the Joanna Briggs Institute case series critical appraisal tool was used for seven studies. Our findings confirm that CIUE is a rare condition (0.7 %). CIUE is associated with decreased live birth rates (53 %), increased recurrent pregnancy loss (23 %), fetal loss beyond 22 weeks gestation (25 %), a higher prevalence of autoimmune diseases (14 %), and a recurrence rate of 30 % in subsequent pregnancies. Moreover, individuals with CIUE had higher rates of pregnancy complications, including gestational hypertension (19 %), intrauterine growth restriction (45 %), and preterm births (43 %). No significant improvement in live birth rate was observed among treated CIUE patients; however, caution is warranted when interpreting these findings due to the limited sample size. Future research in CIUE is crucial given its rarity and complexity.
PubMed: 38941926
DOI: 10.1016/j.jri.2024.104285 -
Blood Advances Jun 2024Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. While studies suggest an overall protective effect of LMWH in...
Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. While studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in preeclampsia remains controversial. LMWH may convey beneficial effects in preeclampsia independent of their anti-coagulant activity, possibly by inhibiting inflammation. Here we evaluated whether LMWH inhibit placental thrombo-inflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle (EV)-induced and platelet-dependent preeclampsia-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation and improves trophoblast proliferation in-vivo and in-vitro. Moreover, LMWH inhibits platelet independent trophoblast NLRP3 inflammasome activation. Mechanistically, LWMH activates via Heparin binding epidermal growth factor (HBEGF) signaling the PI3-Kinase-AKT pathway in trophoblasts thus preventing inflammasome activation. In human preeclampsia placental explants, inflammasome activation and PI3-Kinase-AKT signaling events were reduced with LMWH treatment compared to those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates preeclampsia-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in preeclampsia and identify a signaling mechanism through which LMWH ameliorates preeclampsia, thus providing a rationale for the use of LMWH in preeclampsia.
PubMed: 38941535
DOI: 10.1182/bloodadvances.2023011895 -
Science Advances Jun 2024Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using...
Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions. In an independent dataset, the TRN model predicted target gene expression with an out-of-sample greater than 0.25 for 73% of target genes. We performed siRNA knockdowns of four TFs and achieved concordance between the predicted gene targets in our TRN and differences in expression of knockdowns with an accuracy of >0.7 for three of the four TFs. Our final model contained 113,158 interactions across 391 TFs and 7712 target genes and is publicly available. We identified 29 TFs which were significantly enriched as regulators for genes previously associated with preterm birth, and eight of these TFs were decreased in preterm placentas.
Topics: Humans; Placenta; Female; Pregnancy; Gene Regulatory Networks; Transcription Factors; Genome, Human; Transcriptome; Gene Expression Regulation; Gene Expression Profiling
PubMed: 38941464
DOI: 10.1126/sciadv.adf3411 -
Medicine Jun 2024To analyze maternal and neonatal effects of placental abruption (PA) through a novel classification in the presence of hypertension. Initial hemoglobin parameters were... (Comparative Study)
Comparative Study Observational Study
To analyze maternal and neonatal effects of placental abruption (PA) through a novel classification in the presence of hypertension. Initial hemoglobin parameters were also compared to predict pregnancy outcomes in addition to hypertension. This retrospective cohort designed study was conducted on 115 pregnant women with PA. The main parameters scanned and recorded from the hospital database and patient medical files. Two groups were classified regarding of presence or absence of hypertension (53 hypertensive, 62 normotensive). Maternal demographical and clinical characteristics (abdominal pain, vaginal bleeding) were recorded. APGAR scores below 5 at 1st and 5th minute, fetal or neonatal death, admission and length of stay in Neonatal Intensive Care Unit were also investigated and compared between the groups. Stillborn to live-born ratio and lower APGAR scores < 5 at 5th minute were significantly higher in hypertensive group than normotensive group (P = .006 and 0.047, respectively). Poor maternal outcomes were detected in the hypertensive group than normotensive group regarding rate of blood transfusion (27/53, 50.9%; 18/62, 29%, respectively, P = .017). More abdominal pain and less vaginal bleeding were seen in PA with HT. Higher lymphocyte count, mean platelet volume, and platelet distribution width were reported in hypertensive group. Poorer maternal and neonatal outcomes of hypertensive patients with PA were detected. These patients should deserve greater attention to assess not only the possible risks associated with abruption but also the accompanying complications.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Adult; Abruptio Placentae; Pregnancy Outcome; Infant, Newborn; Apgar Score; Hypertension, Pregnancy-Induced; Hypertension
PubMed: 38941372
DOI: 10.1097/MD.0000000000038633 -
Experimental and Therapeutic Medicine Aug 2024Aberrant expression of long non-coding RNAs (lncRNAs) serves a crucial role in the biological function of trophoblasts and contributes to preeclampsia (PE). lncRNA...
Aberrant expression of long non-coding RNAs (lncRNAs) serves a crucial role in the biological function of trophoblasts and contributes to preeclampsia (PE). lncRNA MIR193BHG expression is increased in PE placental tissues. In the present study, the effects of MIR193BHG on the function of trophoblasts were assessed to elucidate its underlying molecular mechanisms. The subcellular localization of MIR193BHG in HTR-8/SVneo human first-trimester extravillous trophoblast cells was determined using a fluorescent hybridization assay and by conducting nucleocytoplasmic separation. The effect of MIR193BHG knockdown or overexpression on proliferation, migration, invasion and apoptosis was evaluated using Cell Counting Kit-8, wound healing, Transwell and flow cytometry assays. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and protein-protein interaction network construction were subsequently performed to screen the downstream molecules regulated by MIR193BHG. Finally, rescue experiments were conducted to ascertain whether MIR193BHG influenced the biological function of trophoblasts via p53. MIR193BHG was predominantly localized in the nucleus of HTR-8/SVneo cells and overexpression of MIR193BHG significantly inhibited proliferation, migration and invasion, while increasing the rate of apoptosis of HTR-8/SVneo cells. Knockdown of MIR193BHG had the opposite effect. Furthermore, overexpression of MIR193BHG led to increases in both mRNA and protein levels of p53 compared with the control group, and knockdown of p53 rescued the effects induced by overexpression of MIR193BHG on cell proliferation, migration and invasion, while partially counteracting its effects on apoptosis of HTR-8/SVneo cells. In conclusion, the findings of the present study suggested that MIR193BHG served a critical role in progression of PE by regulating the expression of p53, and may be a novel therapeutic target for PE.
PubMed: 38939173
DOI: 10.3892/etm.2024.12609 -
Journal of Extracellular Biology Jan 2024Placental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated...
Placental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated with pregnancy outcomes, including gestational diabetes mellitus (GDM). However, the effect of changes in the maternal microenvironment on the mechanisms associated with the secretion of EVs from placental cells remains to be fully established. Here, we evaluated the effect of high glucose on proteins associated with the trafficking and release of different populations of EVs from placental cells. BeWo and HTR8/SVneo cells were used as placental models and cultured under 5-mM D-glucose (i.e. control) or 25-mM D-glucose (high glucose). Cell-conditioned media (CCM) and cell lysate were collected after 48 h. Different populations of EVs were isolated from CCM by ultracentrifugation (i.e. pellet 2K-g, pellet 10K-g, and pellet 100K-g) and characterised by Nanoparticle Tracking Analysis. Quantitative proteomic analysis (IDA/SWATH) and multiple reaction monitoring protocols at high resolution (MRM) were developed to quantify 37 proteins related to biogenesis, trafficking/release and recognition/uptake of EVs. High glucose increased the secretion of total EVs across the pellets from BeWo cells, an effect driven mainly by changes in the small EVs concentration in the CCM. Interestingly, no effect of high glucose on HTR8/SVneo cells EVs secretion was observed. High glucose induces changes in proteins associated with vesicle trafficking in BeWo cells, including Heat Shock Protein Family A (Hsp70) Member 9 (HSPA9) and Member 8 (HSPA8). For HTR8/SVneo, altered proteins including prostaglandin F2α receptor regulatory protein (FPRP), RAB5A, RAB35, RAB5B, and RB11B, STAM1 and TSG101. These proteins are associated with the secretion and trafficking of EVs, which could explain in part, changes in the levels of circulating EVs in diabetic pregnancies. Further, we identified that proteins RAB11B, PDCD6IP, STAM, HSPA9, HSPA8, SDCBP, RAB5B, RAB5A, RAB7A and ERAP1 regulate EV release in response to high and low glucose when overexpressed in cells. Interestingly, immunohistochemistry analysis of RAB7A revealed distinct changes in placental tissues obtained from women with normal glucose tolerance (NGT, = 6) and those with GDM ( = 6), influenced by diet or insulin treatment. High glucose regulation of proteins involved in intercellular dynamics and the trafficking of multivesicular bodies to the plasma membrane in placental cells is relevant in the context of GDM pregnancies.
PubMed: 38938672
DOI: 10.1002/jex2.135 -
Frontiers in Medicine 2024Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a... (Review)
Review
Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a less invasive approach to prenatal chromosomal disease screening, providing prospective parents with vital information to better prepare for their potential pregnancy outcomes. NIPT was primarily designed for screening trisomy 13, 18, and 21. However, its scope has since broadened to encompass microdeletions and autosomal dominant monogenic diseases. Conversely, the normalization of NIPT can have unintended consequences. Some patients opt for NIPT without any medical indications, driven by a desire to remain cautious. This over-screening for chromosomal abnormalities can exacerbate pregnancy-related anxiety, as individuals might feel pressured into taking the test unnecessarily. While NIPT can be highly successful when conducted correctly, it is not infallible, and obstetricians play a crucial role in managing patient expectations. This includes providing genetic counseling to individuals with relevant genetic information regarding their personal and family histories. In the context of NIPT, a bioinformatics analysis is performed on a cell-free DNA (cfDNA) sample extracted from the mother's placenta to determine the fetal fraction (FF). This FF measurement is vital for quality control and ensuring statistical confidence in the test results. Raising awareness among clinicians about the significance of FF enhances patient care and alleviate concerns about the possibility of failed NIPT. This paper aims to explore the ongoing debates and more specifically the significance and pitfalls of NIPT on a psychosocial and ethical scale, all while highlighting the importance of genetic counseling.
PubMed: 38938382
DOI: 10.3389/fmed.2024.1388481