Human Placenta Samples Research Articles

Acetyl-CoA metabolism maintains histone acetylation for syncytialization of human placental trophoblast stem cells

During pregnancy, placental-fetal nutrient allocation is crucial for fetal and maternal health. However, the regulatory mechanisms for nutrient metabolism and allocation in placental trophoblasts have remained unclear. Here, we used human first-trimester placenta samples and human trophoblast stem cells (hTSCs) to discover that glucose metabolism is highly active in hTSCs and cytotrophoblasts, but during syncytialization, it decreases to basal levels, remaining necessary for fueling acetyl-CoA and differentiation potential. Acetate supplementation could rescue syncytiotrophoblast fusion from glycolysis deficiency by replenishing acetyl-CoA and maintaining histone acetylation, thus rescuing the activation of syncytialization genes. Even brief glycolysis deficiency could permanently inhibit differentiation potential and promote inflammation, which could also be permanently rescued by brief acetate supplementation invivo. These results suggest that hTSCs retain only basal glycolytic acetyl-CoA metabolism during syncytialization to regulate cell fates via nutrient-responsive histone acetylation, with implications for our understanding of the balance between placental and fetal nutrition.

#2767 Micro(nano)plastics are exposed and bioaccumulated in human fetus—the first evidence from neonatal umbilical cord blood and urine

Abstract Background and Aims At present, the world population problem is increasingly serious, and the impact of environmental pollution on the health of pregnant women and fetuses is a global research focus. Among them, micro(nano)plastics (MNPs), as an emerging pollutant, has been confirmed by several animal experiments and in vitro human cell experiments to have biotoxic effects. Recent studies have shown that MNPs are found in human placenta, amniotic fluid, meconium, and other samples, but there is still a lack of direct evidence that MNPs can enter and bioaccumulate in the fetus. Method To initially explore the actual situation of neonatal exposure to MNPs, this study collected umbilical cord blood samples and postnatal urine samples from 6 healthy fetuses in Chengdu, Sichuan, China, and used pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and laser direct infrared spectroscopy (LDIR) to detect and analyze MNPs in samples. Results With an average abundance of 81.15 (40.71) μg/g, MNPs were found in 6 umbilical cord blood samples by Py-GC/MS. Polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS) and polyamide 66 (PA66), 4 different types of MNPs were found, with PE content being the highest among them. By using LDIR, MNPs were found in 5 umbilical cord blood samples, with an average abundance of 17.39 (18.91) particles/g. Three different types of MNPs were found, they are acrylates (ACR), polyethylene terephthalate (PET) and polypropylene (PP). MNPs particles were detected in 6 urine samples by PY-GC/MS, and the average abundance was 8.42 (4.70) μg/g. Two kinds of MNPs, PE and PVC, were detected, and the content of PE was higher. Conclusion The findings demonstrated that the contents and types of MNPs in umbilical cord blood samples were higher than those in urine samples. The levels of MNPs were correlated with the living habits of pregnant mothers, such as the frequency of ordering take-out food. In this study, through the detection of MNPs in umbilical cord blood and neonatal urine samples, we found the direct evidence of MNPs in the fetus for the first time, further confirmed that MNPs can enter the urine through renal metabolism, preliminarily explored the exposure and bioaccumulation effect of MNPs in the fetus, and analyzed the possible risks and related factors of exposure of MNPs during pregnancy, which provided a theoretical basis for in-depth study of the health impact of MNPs on pregnant women and fetuses.

Detecting SARS-CoV-2 in bats of New Mexico using immunohistochemistry on formalin- fixed, paraffn-embedded tissues

Objectives: The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and its zoonotic origin have raised critical questions regarding the potential role of local bat populations as reservoirs or intermediates for the transmission of this or related coronaviruses to humans. The goal of this project is to investigate the presence and diversity of coronaviruses in bat species native to the Southwest USA. Broadly, this study has two primary aims: (1) to detect antigens of coronaviruses in tissues of local bat populations via histological methods and (2) to perform a molecular screen of coronaviruses in these bats. Methods: Individuals from five bat species were evaluated: Artibeus jamaicensis, Myotis velifer, Antrozous pallidus, Tadarida brasiliensis, and Eptesicus fuscus. All species were local, wild-caught bats, with the exception of Artibeus jamaicensis, which is from a colony established at New Mexico State University (NMSU). Tissue was sourced from bats collected by TJO at NMSU. Bat tissue was fixed with formalin and samples subsequently taken of lung, kidney, nasal epithelium, and uterus. Tissue was further processed and embedded in paraffn wax. The embedded tissue was sectioned via a rotary microtome at 4 μm thickness and mounted onto slides. Slides were stained with general coronavirus anti-nucleocapsid primary antibody and a hematoxylin counterstain to visualize cellular structures. Slides were cover-slipped with DPX mounting medium and observed via light microscopy. Results: The immunohistochemistry protocol was performed on tissue from each of the five bat species investigated and on human placenta samples known to be positive for SARS-CoV-2. The latter was used as positive controls. Putative positive staining was seen in both human placenta and bat tissues. Interestingly, coronavirus was detected in Artibeus jamaicensis samples, an unexpected finding given its status as a laboratory colony. Verification of this putative finding is ongoing. Further work on our samples will determine the genetic identity of the coronaviruses detected and contribute to developing a molecular screen for more effcient detection of coronavirus antigens in local bat tissue. This work will serve as a springboard for further understanding coronavirus ecology and evolution in bats of the US southwest, and it can be used to further inform both local surveillance efforts and public policy surrounding the interaction between humans and animals in the natural environment and in controlled settings. Conclusions: Putative detection of coronavirus antigens was found in tissues from bat samples from the Southwestern USA. Implications for this work include broadening our understanding of the diversity and abundance of coronaviruses in the US. Burrell College; US National Science Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exogenous Hydrogen Sulfide Prevents Necroptosis by Inhibiting p38MAPK Pathway Activation in JEG-3 Trophoblast Cells: A Role in Preeclampsia

Objectives: Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H2S) can inhibit necroptosis of human umbilical vein endothelial cells under the high glucose-induced injury. Whether H2S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study aimed to explore the protective role of H2S in trophoblast cells against necroptosis underlying PE. Design: This is an in vitro experimental study. Participants: A total of 10 pregnant women with severe PE and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available. Methods: The expression and localization of necrotic proteins were assayed in human placenta samples, and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H2S donor) and SB203580 (p38 inhibitor). Results: RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine β-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS. Limitations: In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of PE. Conclusions: We proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8/3 and increased expression of RIPA1 and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H2S protected cytotrophoblasts against ceramide-induced necroptosis via the p38MAPK pathway.

Mitochondrial-targeted antioxidant attenuates preeclampsia-like phenotypes induced by syncytiotrophoblast-specific Gαq signaling.

Syncytiotrophoblast stress is theorized to drive development of preeclampsia, but its molecular causes and consequences remain largely undefined. Multiple hormones implicated in preeclampsia signal via the Gαq cascade, leading to the hypothesis that excess Gαq signaling within the syncytiotrophoblast may contribute. First, we present data supporting increased Gαq signaling and antioxidant responses within villous and syncytiotrophoblast samples of human preeclamptic placenta. Second, Gαq was activated in mouse placenta using Cre-lox and DREADD methodologies. Syncytiotrophoblast-restricted Gαq activation caused hypertension, kidney damage, proteinuria, elevated circulating proinflammatory factors, decreased placental vascularization, diminished spiral artery diameter, and augmented responses to mitochondrial-derived superoxide. Administration of the mitochondrial-targeted antioxidant Mitoquinone attenuated maternal proteinuria, lowered circulating inflammatory and anti-angiogenic mediators, and maintained placental vascularization. These data demonstrate a causal relationship between syncytiotrophoblast stress and the development of preeclampsia and identify elevated Gαq signaling and mitochondrial reactive oxygen species as a cause of this stress.

Xeno-estrogenic activity of real-life mixtures of perfluoroalkylated substances in human placenta homogenates

Humans are simultaneously exposed to complex chemical mixtures, and its combined effect can affect human health. As part of the HBM4EU project, the actual mixture of perfluoroalkylated substances (PFAS) in 25 human placenta samples was extracted by chromatographic methods and assessed for xeno-estrogenic activity using two in-vitro bioassays: the estrogen receptor transactivity and the E-Screen assay. Most of the PFAS extracts displayed xeno-estrogenic activity, in one or both assays. The xeno-estrogenic activities in the two bioassays were not correlated, but both assays showed an overall negative correlation with placenta concentrations of single PFAS. Xeno-estrogenic activities were significantly related to maternal characteristics; being higher in young, smokers and primiparous women, but not with fetal growth (birth weight, birth length, head circumference, gestational age, placenta weight). The presented extraction method can be used to study the combined effect of real-life mixtures of PFAS in relation to health outcomes in large-scale human biomonitoring studies.

Brominated flame retardants and legacy organochlorines in archived human placenta samples: Sex differences, temporal analysis and associations with infant birth weight.

Perinatal exposure to persistent organic pollutants (POPs) has been suggested to play a role in the etiology of adverse pregnancy outcomes. This study evaluated temporal changes in the accumulation of several classes of POPs, including polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and several organochlorine pesticides in human placenta and examined their associations with birth outcomes at delivery. Placental tissues (n = 99) previously collected and archived at the Duke University Medical Center from 2009 to 2015 were analyzed for 22 POPs using gas chromatography mass spectrometry. The mean age of mothers was 30.6 years; 8% of newborns were characterized as low birthweight (<2500 g). Of the 22 POPs targeted in the analysis, only p,p’-DDE, BDE-47 and BDE-100 were detected in more than 50% of the samples, with median concentrations of 0.110, 0.310, and 0.033 ng/g wet weight, respectively. Placental PBDE concentrations generally decreased over time, particularly BDE-47. Placental tissues associated with female infants had significantly higher levels of BDE-100 than placental tissues associated with male infants (p = 0.02) and a similar, but not statistically significant trend was observed for BDE-47 (p = 0.07). Multivariate regression models revealed that placental BDE-47 concentrations were associated with a significantly lower birthweight among male, but not female infants. A similar, although non-statistically significant, trend was observed for other POPs, further suggesting sex-specific associations between gestational exposure to POPs and birthweight.

Electrospun fluorinated carbon nanotubes/silk fibroin composite nanofibers for the analysis of perfluoroalkyl and polyfluoroalkyl substances

Assessment of the exposure risk of perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been of public concern for many years. However, it is a challenging undertaking because of the trace levels of these contaminants in the environment and biological systems. In this work, fluorinated carbon nanotubes/silk fibroin (F-CNTs/SF) nanofibers were for the first time synthesized by electrospinning and evaluated as a new adsorbent in pipette tip-solid-phase extraction to enrich PFASs. The addition of F-CNTs increased the mechanical strength and toughness of the SF nanofibers, thus improving the durability of composite nanofibers. The proteophilicity of silk fibroin formed the basis of the good affinity of this material with PFASs. The adsorption behaviors of PFASs on the F-CNTs/SF were investigated by adsorption isotherm experiments to understand the mechanism of extraction. With analysis using ultrahigh performance liquid chromatography-Orbitrap high-resolution mass spectrometric, low limits of detection (0.006–0.090 μg L−1) and enrichment factors of 13–48 were obtained. Meanwhile, the developed method was successfully applied to the detection of wastewater and human placenta samples. This work provides a new idea for the design of novel adsorbents with proteins integrated in polymer nanostructures, a potential routine and practical monitoring technique for PFASs in environmental and biological samples.

Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex

The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A diabetic state affects maternal and fetal health and may lead to functional alterations of placental metabolism, inflammation, hypoxia, and weight, amplifying the fetal stress. The placental molecular adaptations to the diabetic environment and the adaptive spatio-temporal consequences to elevated glucose or insulin are largely unknown (2). We aimed to identify gene expression signatures related to the diabetic placental pathology of placentas from women with diabetes mellitus. Human placenta samples (n = 77) consisting of healthy controls, women with either gestational diabetes mellitus (GDM), type 1 or type 2 diabetes, and women with GDM, type 1 or type 2 diabetes and superimposed PE were collected. Interestingly, gene expression differences quantified by total RNA sequencing were mainly driven by fetal sex rather than clinical diagnosis. Association of the principal components with a full set of clinical patient data identified fetal sex as the single main explanatory variable. Accordingly, placentas complicated by type 1 and type 2 diabetes showed only few differentially expressed genes, while possible effects of GDM and diabetic pregnancy complicated by PE were not identifiable in this cohort. We conclude that fetal sex has a prominent effect on the placental transcriptome, dominating and confounding gene expression signatures resulting from diabetes mellitus in settings of well-controlled diabetic disease. Our results support the notion of placenta as a sexual dimorphic organ.

Predictive plasma biomarker for gestational diabetes: A case-control study in China

ObjectiveThis study aims to find new plasma biomarkers in early pregnancy. DesignThe original study enrolled 1219 pregnant women. We investigated protein expression profiles of placental tissues from women with GDM (n = 89) and normal glucose tolerance (NGT) (n = 83). Maternal plasma samples between two groups in early and middle pregnancy were used for validation of candidate biomarkers. MethodsDifferentially expressed proteins (DEPs) were identified by label-free quantitative proteomics from human placenta samples between two groups. Several DEPs were validated in plasma by Luminex assays. An automatic biochemical analyzer was used to detect blood lipid indexes. The associations of GAL-3BP with biochemical indicators were demonstrated by Pearson's correlation analysis. Binary logistic regression was used to model potential predictive indicators in early pregnancy of GDM. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of the predictive model and the value of GAL-3BP. Results123 DEPs were found in placenta involved in ribosomal function, pancreatic secretion, oxidative phosphorylation, and inflammatory signaling pathway. Plasma GAL-3BP are significantly higher in women with GDM than NGT in the first (p = 0.008) and second (p = 0.026) trimester, but C9 and VWF have no difference. The predictive value of GAL-3BP in the first trimester of pregnancy (AUC 0.64) is better than that in the second trimester (AUC 0.61), and combined predictive model of TG and GAL-3BP at early pregnancy has greater predictive and diagnostic value for GDM (AUC 0.69) than individual GAL-3BP (AUC 0.64). ConclusionsPlasma TG and GAL-3BP has good predictive and diagnostic value at early pregnancy, suggesting that these two indicators may be used as biomarkers for early prediction and diagnosis of GDM. SignificanceThe advantage of this study is that circulating TG and GAL-3BP might differentiate the progress of women with GDM and normal glucose tolerance (NGT) at the early stage of pregnancy. It is the first study to consider the role of GAL-3BP as an early predictive biomarker in the development of GDM during the whole pregnancy. Another advantage is that volunteers in this study were recruited from two provinces in China to eliminate the impacts of environmental confounders. The similar changes of blood glucose/lipid indicators for women with GDM and NGT in both regions was found in the first and second trimester of pregnancy, which added to the reliability of analytical results.

Plastic and Placenta: Identification of Polyethylene Glycol (PEG) Compounds in the Human Placenta by HPLC-MS/MS System.

The placenta is a crucial interface between the fetus and the maternal environment. It allows for nutrient absorption, thermal regulation, waste elimination, and gas exchange through the mother's blood supply. Furthermore, the placenta determines important adjustments and epigenetic modifications that can change the phenotypic expression of the individual even long after birth. Polyethylene glycol (PEG) is a polyether compound derived from petroleum with many applications, from medicine to industrial manufacturing. In this study, for the first time, an integration of ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry (MS) was used to detect suites of PEG compounds in human placenta samples, collected from 12 placentas, originating from physiological pregnancy. In 10 placentas, we identified fragments of PEG in both chorioamniotic membranes and placental cotyledons, for a total of 36 samples.

C18-modified halloysite as a novel sorbent in matrix solid-phase dispersion for the extraction of bisphenol A and diethylstilbestrol from human placenta.

In the current study, the C18-modified halloysite was fabricated via silylation reaction and subsequently used as sorbent in matrix solid-phase dispersion (MSPD) for the extraction of bisphenol A and diethylstilbestrol from human placenta, followed by high-performance liquid chromatography-tandem mass spectrometry analysis. The as-prepared sorbent was characterized by scanning electron microscopy, energy-dispersive spectrometry, Fourier transform infrared spectroscopy, X-ray diffraction, and thermo-gravimetric analysis. Varied parameters such as methanol concentration in wash solvent, pH and salt concentration in elution solvent, elution volume, and mass ratio of sample to sorbent were optimized. The adsorption capacities of bisphenol A and diethylstilbestrol on the developed C18-modified halloysite were 6.3 and 14.2mgg-1, respectively, higher than those on the commercial C18 silica gel. Under the optimal condition, the average recoveries of bisphenol A and diethylstilbestrol by MSPD varied from 91.0 to 106.0%, and the relative standard deviations were less than 10.6% for human placenta samples. The limits of detection in the human placenta were 0.2μgkg-1 for bisphenol A and diethylstilbestrol. The simple C18-modified halloysite-based MSPD method holds great potential for the determination of trace bisphenol A and diethylstilbestrol in the human placenta and other tissues of pregnant women with high sensitivity, accuracy, and reliability.

Induction of human trophoblast stem-like cells from primed pluripotent stem cells

The placenta is a transient but important multifunctional organ crucial for healthy pregnancy for both mother and fetus. Nevertheless, limited access to human placenta samples and the paucity of a proper in vitro model system have hampered our understanding of the mechanisms underlying early human placental development and placenta-associated pregnancy complications. To overcome these constraints, we established a simple procedure with a short-term treatment of bone morphogenetic protein 4 (BMP4) in trophoblast stem cell culture medium (TSCM) to convert human primed pluripotent stem cells (PSCs) to trophoblast stem-like cells (TSLCs). These TSLCs show not only morphology and global gene expression profiles comparable to bona fide human trophoblast stem cells (TSCs) but also long-term self-renewal capacity with bipotency that allows the cells to differentiate into functional extravillous trophoblasts (EVT) and syncytiotrophoblasts (ST). These indicate that TSLCs are equivalent to genuine human TSCs. Our data suggest a straightforward approach to make human TSCs directly from preexisting primed PSCs and provide a valuable opportunity to study human placenta development and pathology from patients with placenta-related diseases.

On-going consequences of in utero exposure of Pb: An epigenetic perspective.

Epigenetic modifications by toxic heavy metals are one of the intensively investigated fields of modern genomic research. Among a diverse group of heavy metals, lead (Pb) is an extensively distributed toxicant causing an immense number of abnormalities in the developing fetus via a wide variety of epigenetic changes. As a divalent cation, Pb can readily cross the placental membrane and the fetal blood brain barrier leading to far-reaching alterations in DNA methylation patterns, histone protein modifications, and micro-RNA expression. Over recent years, several human cohorts and animal model studies have documented hypermethylation and hypomethylation of developmental genes along with altered DNA methyl-transferase expression by in utero Pb exposure in a dose-, duration-, and sex-dependent manner. Modifications in the expression of specific histone acetyltransferase enzymes along with histone acetylation and methylation levels have been reported in rodent and murine models. Apart from these, down-regulation and up-regulation of certain microRNAs crucial for fetal development have been shown to be associated with in utero Pb exposure in human placenta samples. All these modifications in the developing fetus during the prenatal and perinatal stages reportedly caused severe abnormalities in early or adult age, such as impaired growth, obesity, autism, diabetes, cardiovascular diseases, risks of cancer development, and Alzheimer's disease. In this review, currently available information on Pb-mediated alterations in the fetal epigenome is summarized. Further research on Pb-induced epigenome modification will help to understand the mechanisms in detail and will enable us to formulate safety guidelines for pregnant women and developing children.

Protein Phosphatase 2A Activation Via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome.

[Figure: see text].

Abstract P226: Transcriptome Signature Of Placentas From Diabetic Pregnancies Is Confounded By Fetal Sex.

Hypertension-associated obstetric diseases like diabetes mellitus (DM) or preeclampsia occur in 25-35% of pregnancies and are related to placental dysfunction. The placenta has a unique structure and function to guarantee healthy pregnancy, fetal development, and outcome. Thus, the diabetic environment featuring inflammation, metabolic alterations, and hypoxia, is challenging with increased stress for mother and foetus. Delivery-related complications and adverse post-pregnancy outcomes, for example the increased risk for preeclampsia, are related to placental pathology in the different types of DM. Therefore, understanding disturbed placental development during pathologic pregnancy is important. We hypothesize a placental transcriptome signature present in pathologic pregnancy. We aimed to broaden our understanding of placental adaptations to various forms of diabetic pregnancy. Human placenta samples from healthy controls (n = 29), women with gestational DM (GDM, n = 12), DM type 1 (DM1, n = 17), DM type 2 (DM2, n = 3) and GDM, DM1 or DM2 superimposed by preeclampsia (n = 16) were included. We quantified gene expression by Illumina TruSeq stranded total RNA Sequencing and analyzed data by means of principal component analysis (PCA), differential expression and gene set enrichment. The samples were mainly split by fetal sex in the PCA rather than diabetic subgroups. Genes associated with the principal components were primary located on the male sex chromosome ( Xist, Uty, Usp9y, Ddx3y ) and only weakly enriched in functionally relevant gene sets. The fetal sex was identified as single main explanatory variable when the principal components were associated with clinical patient data. Placentas complicated by DM2 identified 93 and 27 significant differential expressed genes (DEG; adj. p-value &lt; 0.05) in comparison to healthy controls and GDM, respectively. Comparison of DM1 to DM2 or GDM showed four and two significant genes. In this cohort possible effects of GDM and preeclampsia were not observed.We conclude that fetal sex is dominating placental gene expression and confounding transcriptome signatures resulting from diabetes, in settings of well controlled diabetic disease.

Detection of Microplastic in Human Placenta and Meconium in a Clinical Setting.

Environmental pollution with microplastics (MPs) is a major and worldwide concern. Involuntary exposure to MPs by ingestion or inhalation is unavoidable. The effects on human health are still under debate, while in animals, cellular MP translocation and subsequent deleterious effects were shown. First reports indicate a potential intrauterine exposure with MPs, yet readouts are prone to contamination. Method: To establish a thorough protocol for the detection of MPs in human placenta and fetal meconium in a real-life clinical setting, a pilot study was set up to screen for MPs > 50 µm in placental tissue and meconium sampled during two cesarean sections for breech deliveries. After chemical digestion of non-plastic material, Fourier-transform infrared (FTIR) microspectroscopy was used to analyze the presence of 10 common types of microplastic in placenta and stool samples. Results: Human placenta and meconium samples were screened positive for polyethylene, polypropylene, polystyrene, and polyurethane, of which only the latter one was also detected as airborne fallout in the operating room—thus representing potential contamination. Conclusion: We found MPs > 50 µm in placenta and meconium acquired from cesarean delivery. Critical evaluation of potential contamination sources is pivotal and may guide future clinical studies to improve the correct detection of MPs in organ tissue. Studies investigating nano-sized plastics in human tissue are warranted.

Morphometric analysis of Hofbauer cells in normal placenta and chorioamnionitis in humans.

Hofbauer cells are macrophages residing in the stroma of placental villi and play a number of roles during normal pregnancy, as well as pathological conditions. A morphometric analysis of Hofbauer cells, in particular to investigate the number of cells, their size and shape in samples of normal human placenta from 1st trimester, term and with chorioamnionitis was performed. Tissue samples were immunostained for CD206 antigen and evaluated using ImageJ software. We detected significant changes in number and morphology of HBCs between normal placenta and placenta with chorioamnionitis samples. In chorioamnionitis, the cells were unevenly distributed within the villi, generally present in higher numbers, larger and more elongated than those in normal 1st trimester and term placenta.

Comparison of extraction methods for per- and polyfluoroalkyl substances (PFAS) in human serum and placenta samples\u2014insights into extractable organic fluorine (EOF)

Since the detection of per- and polyfluoroalkyl substances (PFAS) in humans and different environmental media in the last two decades, this substance group has attracted a lot of attention as well as increasing concerns. The fluorine mass balance approach, by comparing the levels of targeted PFAS after conversion to fluorine equivalents with those of extractable organic fluorine (EOF), showed the presence of unidentified organofluorine in different environmental samples. Out of the thousands of PFAS in existence, only a very small fraction is included in routine analysis. In recent years, liquid chromatography coupled with tandem-mass spectrometry (LC-MS/MS) has demonstrated the ability to analytically cover a wide spectrum of PFAS. In contrast, conventional extraction methods developed 10 to 15 years ago were only evaluated for a limited number of PFAS. The aim of the present study was to evaluate the advantages and disadvantages of three different extraction methods, adapted from the literatures without further optimization (ion-pair liquid-liquid extraction, solid-phase extraction (SPE), using hydrophilic-lipophilic (HLB) or weak anion exchange (WAX) sorbents), for human biomonitoring of 61 PFAS in serum and placental tissue samples. In addition, levels of EOF were compared among these extraction methods via spiked samples. Results showed that performance, in terms of recovery, differed between the extraction methods for different PFAS; different extraction methods resulted in different EOF concentrations indicating that the choice of extraction method is important for target PFAS and EOF analysis. Results of maternal serum samples, analyzed in two different laboratories using two different extraction methods, showed an accordance of 107.6% (± 21.3); the detected perfluoroalkyl acids (PFAAs) in maternal and cord serum samples were in the range of 0.076 to 2.9 ng/mL.Graphical abstract

Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes.

Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human placenta samples from an endemic area and ablating inflammasome components in a PM mouse model. The reduction in birth weight in babies from infected mothers is paralleled by increased placental expression of AIM2 and NLRP3 inflammasomes. Using genetic dissection, we reveal that inflammasome activation pathways are involved in the production and detrimental action of interleukin-1β (IL-1β) in the infected placenta. The IL-1R pharmacological antagonist Anakinra improved pregnancy outcomes by restoring fetal growth and reducing resorption in an experimental model. These findings unveil that IL-1β-mediated signaling is a determinant of PM pathogenesis, suggesting that IL-1R antagonists can improve clinical outcomes of malaria infection in pregnancy.