Functional variation among mesenchymal stem cells derived from different tissue sources.

Background: Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent variability, which is influenced by various factors, such as the tissue source, culture conditions, and passage number. Methods: MSCs were sourced from clinically relevant tissues, including adipose tissue-derived MSCs (ADMSCs, n = 2), chorionic villi-derived MSCs (CMMSCs, n = 2), amniotic membrane-derived MSCs (AMMSCs, n = 3), and umbilical cord-derived MSCs (UCMSCs, n = 3). Passages included the umbilical cord at P0 (UCMSCP0, n = 2), P3 (UCMSCP3, n = 2), and P5 (UCMSCP5, n = 2) as well as the umbilical cord at P5 cultured under low-oxygen conditions (UCMSCP5L, n = 2). Results: We observed that MSCs from different tissue origins clustered into six distinct functional subpopulations, each with varying proportions. Notably, ADMSCs exhibited a higher proportion of subpopulations associated with vascular regeneration, suggesting that they are beneficial for applications in vascular regeneration. Additionally, CMMSCs had a high proportion of subpopulations associated with reproductive processes. UCMSCP5 and UCMSCP5L had higher proportions of subpopulations related to female reproductive function than those for earlier passages. Furthermore, UCMSCP5L, cultured under low-oxygen (hypoxic) conditions, had a high proportion of subpopulations associated with pro-angiogenic characteristics, with implications for optimizing vascular regeneration. Conclusions: This study revealed variation in the distribution of MSC subpopulations among different tissue sources, passages, and culture conditions, including differences in functions related to vascular and reproductive system regeneration. These findings hold promise for personalized regenerative medicine and may lead to more effective clinical treatments across a spectrum of medical conditions.

Intravenous Immunoglobulins for Recurrent Chronic Histiocytic Intervillositis: A Series of Case Studies.

INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases. PATIENTS AND METHODS: We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients. RESULTS: For three patients, intravenous immunoglobulins were initiated at the ßHCG positivity at 1 g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG. CONCLUSION: This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.

Plasmodium falciparum alters the trophoblastic barrier and stroma villi organization of human placental villi explants.

BACKGROUND: The sequestration of Plasmodium falciparum infected erythrocytes in the placenta, and the resulting inflammatory response affects maternal and child health. Despite existing information, little is known about the direct impact of P. falciparum on the placental barrier formed by trophoblast and villous stroma. This study aimed to assess placental tissue damage caused by P. falciparum in human placental explants (HPEs). METHODS: HPEs from chorionic villi obtained of human term placentas (n = 9) from normal pregnancies were exposed to P. falciparum-infected erythrocytes (IE) for 24 h. HPEs were embedded in paraffin blocks and used to study tissue damage through histopathological and histochemical analysis and apoptosis using TUNEL staining. Culture supernatants were collected to measure cytokine and angiogenic factors and to determine LDH activity as a marker of cytotoxicity. A subset of archived human term placenta paraffin-embedded blocks from pregnant women with malaria were used to confirm ex vivo findings. RESULTS: Plasmodium falciparum-IE significantly damages the trophoblast layer and the villous stroma of the chorionic villi. The increased LDH activity and pathological findings such as syncytial knots, fibrin deposits, infarction, trophoblast detachment, and collagen disorganization supported these findings. The specific damage to the trophoblast and the thickening of the subjacent basal lamina were more pronounced in the ex vivo infection. In contrast, apoptosis was higher in the in vivo infection. This disparity could be attributed to the duration of exposure to the infection, which significantly varied between individuals naturally exposed over time and the 24-h exposure in the ex vivo HPE model. CONCLUSION: Exposure to P. falciparum-IE induces a detachment of the syncytiotrophoblast, disorganization of the stroma villi, and an increase in apoptosis, alterations that may be associated with adverse results such as intrauterine growth restriction and low birth weight.

Association between concentrations of rare earth elements in chorionic villus and risk for unexplained spontaneous abortion.

Rare earth elements (REEs) exposure during pregnancy may increase the risk of unexplained spontaneous abortion. However, the association between REEs intrauterine exposure and unexplained spontaneous abortion had yet to be studied. In order to conduct this large case-control study, we thus collected chorionic villus from 641 unexplained spontaneous abortion and 299 control pregnant women and detected the concentrations of 15 REEs by inductively coupled plasma mass spectrometer (ICP-MS). Because the detection rates of 10 REEs were less than 80%, the remaining 5 REEs, which were lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd) and yttrium (Y), underwent to further analysis. The association between 5 REEs and unexplained spontaneous abortion was assessed by using the logistic regression, bayesian kernel regression (BKMR) and weighted quantile sum regression (WQS) models. In the adjusted logistic regression model, Pr, Nd and Y enhanced the incidence of unexplained spontaneous abortion in a dose-dependent way and Ce increased the risk only at high concentration group. The result of BKMR model demonstrated that the risk of unexplained spontaneous abortion increased as the percentile of five mixed REEs increased. Y and Nd were both significantly associated with an increased incidence of unexplained spontaneous abortion, but La was correlated with a decrease in the risk of unexplained spontaneous abortion. Pr was substantially associated with an increase in the risk of unexplained spontaneous abortion when other REEs concentrations were fixed at the 25th and 50th percentiles. According to WQS regression analysis, the WQS index was significantly associated with unexplained spontaneous abortion (OR = 3.75, 95% CI:2.40-5.86). Y had the highest weight, followed by Nd and Pr, which was consistent with the analysis results of our other two models. In short, intrauterine exposure to REEs was associated with an increased risk of unexplained spontaneous abortion, with Y, Nd and Pr perhaps playing an essential role.

Transcriptomic analysis reveals the anti-cancer effect of gestational mesenchymal stem cell secretome.

The environment created during embryogenesis contributes to reducing aberrations that drive structural malformations and tumorigenesis. In this study, we investigate the anti-cancer effect of mesenchymal stem cells (MSCs) derived from 2 different gestational tissues, the amniotic fluid (AF) and the chorionic villi (CV), with emphasis on their secretome. Transcriptomic analysis was performed on patient-derived AF- and CV-MSCs collected during prenatal diagnosis and identified both mRNAs and lncRNAs, involved in tissue homeostasis and inhibiting biological processes associated with the etiology of aggressive cancers while regulating immune pathways shown to be important in chronic disorders. Secretome enrichment analysis also identified soluble moieties involved in target cell regulation, tissue homeostasis, and cancer cell inhibition through the highlighted Wnt, TNF, and TGF-ß signaling pathways. Transcriptomic data were experimentally confirmed through in vitro assays, by evaluating the anti-cancer effect of the media conditioned by AF- and CV-MSCs and the exosomes derived from them on ovarian cancer cells, revealing inhibitory effects in 2D (by reducing cell viability and inducing apoptosis) and in 3D conditions (by negatively interfering with spheroid formation). These data provide molecular insights into the potential role of gestational tissues-derived MSCs as source of anti-cancer factors, paving the way for the development of therapeutics to create a pro-regenerative environment for tissue restoration following injury, disease, or against degenerative disorders.

Convergently evolved placental villi show multiscale structural adaptations to differential placental invasiveness.

Despite having a single evolutionary origin and conserved function, the mammalian placenta exhibits radical structural diversity. The evolutionary drivers and functional consequences of placental structural diversity are poorly understood. Humans and equids both display treelike placental villi, however these villi evolved independently and exhibit starkly different levels of invasiveness into maternal tissue (i.e. the number of maternal tissue layers between placental tissue and maternal blood). The villi in these species therefore serve as a compelling evolutionary case study to explore whether placentas have developed structural adaptations to respond to the challenge of reduced nutrient availability in less invasive placentas. Here, we use three-dimensional X-ray microfocus computed tomography and electron microscopy to quantitatively evaluate key structures involved in exchange in human and equid placental villi. We find that equid villi have a higher surface area to volume ratio and deeper trophoblastic vessel indentation than human villi. Using illustrative computational models, we propose that these structural adaptations have evolved in equids to boost nutrient transfer to compensate for reduced invasiveness into maternal tissue. We discuss these findings in relation to the 'maternal-fetal conflict hypothesis' of placental evolution.

HOTAIR/miR-1277-5p/FBN2 signaling axis is involved in recurrent spontaneous abortion by regulating the growth, migration, and invasion of HTR-8/SVneo cells†.

OBJECTIVE: This study aimed to explore the specific pathways by which HOX transcript antisense intergenic RNA contributes to the pathogenesis of unexplained recurrent spontaneous abortion. METHODS: Real-time quantitative PCR was employed to assess the differential expression levels of HOX transcript antisense intergenic RNA in chorionic villi tissues from unexplained recurrent spontaneous abortion patients and women with voluntarily terminated pregnancies. HTR-8/SVneo served as a cellular model. Knockdown and overexpression of HOX transcript antisense intergenic RNA in the cells were achieved through siRNA transfection and pcDNA3.1 transfection, respectively. Cell viability, migration, and invasion were evaluated using cell counting kit-8, scratch, and Transwell assays, respectively. The interaction among the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 axis was predicted through bioinformatics analysis and confirmed through in vitro experiments. Furthermore, the regulatory effects of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis on cellular behaviors were validated in HTR-8/SVneo cells. RESULTS: We found that HOX transcript antisense intergenic RNA was downregulated in chorionic villi tissues from unexplained recurrent spontaneous abortion patients. Overexpression of HOX transcript antisense intergenic RNA significantly enhanced the viability, migration, and invasion of HTR-8/SVneo cells, while knockdown of HOX transcript antisense intergenic RNA had the opposite effects. We further confirmed the regulatory effect of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis in unexplained recurrent spontaneous abortion. Specifically, HOX transcript antisense intergenic RNA and fibrillin 2 were found to reduce the risk of unexplained recurrent spontaneous abortion by enhancing cell viability, migration, and invasion, whereas miR-1277-5p exerted the opposite effects. CONCLUSION: HOX transcript antisense intergenic RNA promotes unexplained recurrent spontaneous abortion development by targeting inhibition of miR-1277-5p/fibrillin 2 axis.

Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease.

Tumor necrosis factor-α (TNF-α) antagonists are highly effective in controlling autoimmune diseases. This has led to speculation that they might also be useful in treating inflammatory placental conditions, such as chronic villitis of unknown etiology (VUE). VUE affects 10-15% of term placentas and is associated with recurrent fetal growth restriction (FGR) and pregnancy loss. We aimed to evaluate outcomes in patients with autoimmune diseases with and without anti-TNF-α biologic exposure during gestation. This retrospective cohort study compared pregnant women with autoimmune disease taking anti-TNF-α biologics (n = 89) to pregnant women with autoimmune disease but not taking a biologic (n = 53). We extracted data on all patients meeting our inclusion criteria over a 20-year period. Our primary outcome was the diagnosis of VUE by histology. Our secondary outcomes were maternal and neonatal complications such as preeclampsia, FGR, and neonatal intensive care admission. Kruskal-Wallis and chi-squared tests were performed as appropriate for statistical analysis. Maternal characteristics were comparable between groups, and there was no increase in adverse pregnancy outcomes based on anti-TNF-α treatment. Exposure to anti-TNF-α therapy had no significant effect on the incidence of VUE or other obstetric complications. Within the cohort exposed to anti-TNF-α biologics during pregnancy, the rate of VUE was 9.3%, which is comparable to the reported general population risk. Our data support the safety profile of biologic use in pregnancy.

Massive perivillous fibrin deposition: Diagnosis, obstetrical features, and treatment.

MPVFD (Massive perivillous fibrin deposition) is placental lesion characterized by extensive massive deposits of fibrin in the intervillous space, extending over at least 25 % of the placental volume. Currently, this pathology can only be detected through histopathological examination of the placenta after a pregnancy has ended. The underlying mechanisms are poorly studied, there is no biomarker available for the diagnosis of MPVFD and treatment protocols are experimental and still lacking. The objective of this study is to systematically review the literature on the associated clinicopathologic features, treatment, and prognosis of MPVFD. We ended up with 17 studies, of these 12 studies were considered relevant for this article and included in the final analysis. All studies reporting MPVFD are retrospective. MPVFD is associated with recurrent miscarriage, intra uterine fetal death (IUFD), intra uterine growth restriction (IUGR) and preterm delivery. The prevalence in pregnancies with a delivery after 22 weeks of gestation was at 1.1 % and even higher to 2.7 % in recurrent early miscarriages. The reported risk of fetal death in MPVFD ranges mainly from 15 to 80 %. Preterm delivery is spontaneous in 50 to 70 % of cases and induced by of a severe intrauterine growth restriction (IUGR) in 30 to 50 % of cases depending on the study. Its causes and treatment are still poorly understood, although several avenues have been explored. This review summarizes current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology, and potential prophylaxis against recurrence in this chronic inflammatory placental syndrome.

The normality of the first-trimester placentae collected from elective terminations.

Placentae collected from elective terminations during the first trimester are commonly used as control samples in research. However, it is widely acknowledged that many complications of pregnancies can occur or originate during the early stage of gestation. This raises the question that the placentae collected from the first trimester may not accurately reflect normal placental conditions. In this study, 95 placentae were collected from elective terminations and histology was performed. Out of these, 53 placentae (56 %) exhibited the typical structure of placental villi, indicating normal development. However, 42 placentae (44 %) showed placental hydrops, with varying degrees of severity (mild, moderate, or severe). Placental hydrops has been linked to several complicated pregnancies in the later stages of gestation. Our findings suggest that the development of pregnancy pathologies could start in the first trimester, as observed by the presence of hydrops. Placental researchers should be aware of when using first-trimester placentae from termination as controls in studies. However, it remains unclear whether pathological morphologies resolve or ameliorate as the pregnancy progression or whether such placentae continue to have such pathology, but clinical symptoms/signs do not manifest.

Genetic analysis of chorionic villus tissues in early missed abortions.

Chromosomal abnormalities are the most common etiology of early spontaneous miscarriage. However, traditional karyotyping of chorionic villus samples (CVSs) is limited by cell culture and its low resolution. The objective of our study was to investigate the efficiency of molecular karyotyping technology for genetic diagnosis of early missed abortion tissues. Chromosome analysis of 1191 abortion CVSs in early pregnancy was conducted from August 2016 to June 2021; 463 cases were conducted via copy-number variations sequencing (CNV-seq)/quantitative fluorescent-polymerase chain reaction (QF-PCR) and 728 cases were conducted using SNP array. Clinically significant CNVs of CVSs were identified to clarify the cause of miscarriage and to guide the couples' subsequent pregnancies. Among these, 31 cases with significant maternal cell contamination were removed from the study. Among the remaining 1160 samples, 751 cases (64.7%) with genetic abnormalities were identified, of which, 531 (45.8%) were single aneuploidies, 31 (2.7%) were multiple aneuploidies, 50 (4.3%) were polyploidies, 54 (4.7%) were partial aneuploidies, 77 (6.6%) had submicroscopic CNVs (including 25 with clinically significant CNVs and 52 had variants of uncertain significance), and 8 cases (0.7%) were uniparental disomies. Our study suggests that both SNP array and CNV-seq/QF-PCR are reliable, robust, and high-resolution technologies for genetic diagnosis of miscarriage.

Impact of villitis of unknown etiology and adverse acute neonatal outcomes in Eastern Ontario.

INTRODUCTION: Villitis of unknown etiology (VUE) is a histopathological lesion associated with adverse neonatal outcomes. We seek to define the obscure relationship between the severity and distribution of VUE and adverse neonatal outcomes. METHODS: A retrospective chart review was conducted of pathologic findings from singleton placentas diagnosed with VUE between 2013 and 2019. Control placentas were matched 1:1 for gestational age and presence/absence of fetal IUGR. Neonatal outcomes of interest included: newborn resuscitation, NICU admission, Apgar scores and cord blood acidosis. Odds ratio and 95 % confidence intervals were calculated with controls as the reference. RESULTS: 452 placentas were included. 35 % of pregnancies were complicated by IUGR. When analyzed by severity (low-grade: OR = 4.75 [2.86-8.14]; high-grade: OR = 4.76 [2.71-8.79]) and distribution (focal: OR = 5.24 [2.87-10.17]; multifocal: OR = 4.90 [2.90-8.59]), VUE was significantly associated with need for newborn resuscitation. No other neonatal outcomes of interest were significantly associated with VUE diagnosis. DISCUSSION: We determined a statistically significant association between VUE severity and distribution and the need for newborn resuscitation. VUE lesions were not associated with any additional neonatal outcomes of interest. Further studies with larger sample sizes are required to confirm these associations for obstetric and neonatal case management.

Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage.

BACKGROUND: It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. METHODS: Placental villi of elective terminations of pregnancies (ETPs) and miscarriage were collected. Proliferative activity and apoptosis of villi trophoblasts and angiogenesis were detected by TUNEL and immunochemistry. The expressions of thyroid hormone receptors (THRs), transthyretin (TTR), monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptides 1A1 (OATP1A1), deiodinase 2 (Dio2) and Dio3 were examined by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. JEG3 cell was treated with iopanoic acid (IOP), an inhibitor of Dio2 activity, the expressions of Dio2, placenta growth factor (PLGF) and sFlt1 were detected by RT-PCR and Western blot. RESULTS: Cell proliferation was suppressed and apoptosis was increased in placental villi cytotrophoblasts of miscarriage. CD34+ vessel number and vascular endothelial growth factor (VEGF) protein abundance were decreased in miscarriage. In miscarriage group, the gene expression of Dio2, Dio3, TTR and THRα, but not THRß, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRß. The protein abundance of Dio2 in miscarriage villi was decreased compared with that in ETP. In JEG3 cells, the gene expression of PLGF was decreased and the expression of sFlt1 was increased in IOP treatment; The protein abundance of Dio2 was downregulated but the gene expression of Dio2 was unaffected in IOP treatment. CONCLUSION: Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.

Modeling the Progression of Placental Transport from Early- to Late-Stage Pregnancy by Tuning Trophoblast Differentiation and Vascularization.

The early-stage placental barrier is characterized by a lack of fetal circulation and by a thick trophoblastic barrier, whereas the later-stage placenta consists of vascularized chorionic villi encased in a thin, differentiated trophoblast layer, ideal for nutrient transport. In this work, predictive models of early- and late-stage placental transport are created using blastocyst-derived placental stem cells (PSCs) by modulating PSC differentiation and model vascularization. PSC differentiation results in a thinner, fused trophoblast layer, as well as an increase in human chorionic gonadotropin secretion, barrier permeability, and secretion of certain inflammatory cytokines, which are consistent with in vivo findings. Further, gene expression confirms this shift toward a differentiated trophoblast subtype. Vascularization results in a molecule type- and size-dependent change in dextran and insulin permeability. These results demonstrate that trophoblast differentiation and vascularization have critical effects on placental barrier permeability and that this model can be used as a predictive measure to assess fetal toxicity of xenobiotic substances at different stages of pregnancy.

Automated stereological image analysis approach of the human placenta: Surface areas and vascularization.

Detecting and quantifying surface densities of placental villi and their vasculature adds important information on the development of the placenta under different exposures and pathological conditions. Today, a larger number of samples and tissue areas can be examined using automated Artificial Intelligence-based approaches. Although each image series calls for a particular approach, sharing the methods will help in facilitating reproducibility and comparability. Here we show the protocol of a software-based quantification of vessels (number and area) in villous tissues of human placentas, based on scanned images of full-size placental sections.

Transcriptomic analysis of stem cells from chorionic villi uncovers the impact of chromosomes 2, 6 and 22 in the clinical manifestations of Down syndrome.

BACKGROUND: Down syndrome (DS) clinical multisystem condition is generally considered the result of a genetic imbalance generated by the extra copy of chromosome 21. Recent discoveries, however, demonstrate that the molecular mechanisms activated in DS compared to euploid individuals are more complex than previously thought. Here, we utilize mesenchymal stem cells from chorionic villi (CV) to uncover the role of comprehensive functional genomics-based understanding of DS complexity. METHODS: Next-generation sequencing coupled with bioinformatic analysis was performed on CV obtained from women carrying fetuses with DS (DS-CV) to reveal specific genome-wide transcriptional changes compared to their euploid counterparts. Functional assays were carried out to confirm the biological processes identified as enriched in DS-CV compared to CV (i.e., cell cycle, proliferation features, immunosuppression and ROS production). RESULTS: Genes located on chromosomes other than the canonical 21 (Ch. 2, 6 and 22) are responsible for the impairment of life-essential pathways, including cell cycle regulation, innate immune response and reaction to external stimuli were found to be differentially expressed in DS-CV. Experimental validation confirmed the key role of the biological pathways regulated by those genes in the etiology of such a multisystem condition. CONCLUSIONS: NGS dataset generated in this study highlights the compromised functionality in the proliferative rate and in the innate response of DS-associated clinical conditions and identifies DS-CV as suitable tools for the development of specifically tailored, personalized intervention modalities.

Pro-inflammatory cytokines are modified during the multiplication of Trypanosoma cruzi within the placental chorionic villi and are associated with the level of infection via the signaling pathway NF-κB.

PROBLEM: Congenital Trypanosoma cruzi (T. cruzi) infection has been associated with changes in the levels of TNF-α and IFN-γ during the pregnancy. Therefore, we propose to study the participation and dynamics of proinflammatory cytokines in the infection process of placental explants infected by T. cruzi in vitro. METHOD OF STUDY: Chorionic villous explants (CVE) obtained of human term placentas (n = 8) from normal pregnancies were cultured with 105 trypomastigotes/mL of Tulahuen strain DTU VI for 0, 2, 4, 16, 24, 48 and 72 h. Explants were treated with sulfasalazine (SULF) (5 mM) and N-acetyl-cysteine (NAC) (15 mM), as inhibitors molecules of NF-κB pathway, or LPS (1 µg/mL) for 24 and 72 h p.i. Motile trypomastigotes were counted in culture supernatants. Immunohistochemistry and ELISA for TNF-α, IFN-γ, IL-1ß, IL-4, and IL-10 were performed in CVE and culture supernatants respectively. The parasite load was measured by RT-qPCR. RESULTS: T. cruzi invades the chorionic villi from 4 h p.i. increasing significantly its DNA at 48 and 72 h p.i. of culture (parasite multiplication phase). They were detected in stromal cells, which was related to elevation of TNF-α, IL-1ß, IFN-γ, and IL-10. The inhibition of NF-κB activity in the explants decreased the production of the analyzed cytokines, showing elevated levels of T. cruzi DNA during the multiplication phase of the parasite. CONCLUSIONS: Placental tissue modifies the secretion of pro-inflammatory cytokines during the phase of parasite multiplication, but not during the invasion phase, which in turns modifies the level of infection via the signaling pathway NF-κB.

FOXP3-positive cell infiltration in the chorionic villi is increased in the placenta accreta and decreased in the placental abruption.

OBJECTIVES: Growing data suggest a role of Treg cells in placentation. The aim of the study was to evaluate Treg cells (FOXP3-positive cells) placental bed infiltration in patients with placenta accrete syndrome (PAS) and patients who experienced placental abruption. MATERIAL AND METHODS: The study group included 13 patients with PAS and the control group consisted of 66 women who had caesarean (CD) delivery of whom, 44 patients with elective caesarean (EC) delivery, and 22 patients with urgent caesarean (UC) delivery due to placental abruption. FOXP3 cell infiltration was assessed by means of immunohistochemistry in placental chorionic villous (CV) and in the decidua (D) and cumulatively in the placental bed (PB). RESULTS: We observed significant difference in the degree of FOXP3-positive cell CV infiltration between studied groups (p = 0.04). FOXP3-positive cells were the most commonly observed in PAS patients, while, they were the least frequently presented in patients after UC. The immunoreactivity for FOXP3-positive cells in CV were as follows: PAS 5 (38%), urgent CS 1 (5%) and elective CS 8 (18%) subjects. We found no difference in the presence of FOXP3-positive cells in the D (p = 0.35) and in the PB (p = 0.23) of analyzed groups. FOXP3-cell infiltration was not related with patient age, BMI, gestational age and neonatal birth weight. CONCLUSIONS: Our study provides further evidence that abnormal invasive placentation is an associated disturbance of the maternal immune response. Accordingly, we have theorized that alteration of the FOXP3-positive Treg cell infiltration into the placental bed allows trophoblast cell invasion.

Investigation of Beclin 1 and TNF-α expressions in preeclampsia placentas: Immunohistochemical study.

BACKGROUND: Preeclampsia is a pregnancy complication Aim of this study was to investigate expression of Beclin1 and tumor necrosis factor (TNF)-α in normotensive and preeclamptic placentas of pregnant women patients. METHODS: Twenty normotensive and 20 preeclamptic patients placentas were dissected for paraffin- wax processing. Placental samples were embedded in parafin blocks. Sections were stained with Hematoxylin-Eosin staining and TNF-α and Beclin1 immunostaining. RESULTS: In control group, root and floating villi were normal in histological perspectives, syncytial node number was low, vessels were normal with connective tissue. No hemorrhage was observed in the intervillous area. In preeclampsia group, decidual cell degeneration and fibrinoid accumulation increased. Vascular dilatation and congestion with mononuclear cell infiltration were observed. Beclin1 reaction was generally negative in control group. In preeclampsia group, Beclin1 reaction was increased in decidual cells, syncytial nodes and bridges and in chorionic villi and in some Hoffbauer cells. In control group, TNF-α expression was mainly negative but only in some decidual cells. In preeclampsia, TNF-α reaction was observed in degenerated decidua cells, in leukocytes and in villi. CONCLUSION: In preeclampsia placentas, degenerated decidua cells and inflammation increased. It was thought that Beclin1 and TNF-α signals could be used as a marker in affecting the fetal structure of blood flow in preeclamptic placentas.

Generating Functional Multicellular Organoids from Human Placenta Villi.

The interaction between trophoblasts, stroma cells, and immune cells at the maternal-fetal interface constitutes the functional units of the placenta, which is crucial for successful pregnancy outcomes. However, the investigation of this intricate interplay is restricted due to the absence of efficient experimental models. To address this challenge, a robust, reliable methodology for generating placenta villi organoids (PVOs) from early, late, or diseased pregnancies using air-liquid surface culture is developed. PVOs contain cytotrophoblasts that can self-renew and differentiate directly, along with stromal elements that retain native immune cells. Analysis of scRNA sequencing and WES data reveals that PVOs faithfully recapitulate the cellular components and genetic alterations of the corresponding source tissue. Additionally, PVOs derived from patients with preeclampsia exhibit specific pathological features such as inflammation, antiangiogenic imbalance, and decreased syncytin expression. The PVO-based propagation of primary placenta villi should enable a deeper investigation of placenta development and exploration of the underlying pathogenesis and therapeutics of placenta-originated diseases.