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Objective To explore the regulative mechanism of hypoxia/reoxygen (H/R) for invasion ability of extravillous trophoblast (EVT). Methods Immortalized human EVT cell line HTR-8/SVneo in early pregnancy, primary EVT cells isolated from the villi of placenta in early pregnancy, and villi explants were cultured respectively. A simulation model of H/R environment in EVT cells invading the uterus was established under the conversion conditions of 1% O2 for 24 h to 20% O2 for another 24 h. Western blotting and immunofluorescence assay were used to detect the expression of key factors such as cell invasion, and Transwell chamber test was employed to observe cell migration and invasion. Results After H/R induction, the migration and invasion abilities of HTR-8/SVneo cells were weakened, and the epitaxial ability of cultured villi explants and the migration and invasion abilities of isolated primary EVT cells were also weakened. Under H/R conditions, the expression levels of MMP-2 and MMP-9, integrin-β1 and integrin-α5 were decreased in HTR-8/SVneo cells (P < 0.05), and the protein expression of DNA methyltransferase (DNMTs) was also down-regulated (P < 0.01). In the primary EVT cells under H/R condition, the expression levels of epithelial-mesenchymal transition (EMT) positive regulatory factors, Slug and Snails, were inhibited (P < 0.05), that of epithelial cell marker E-cadherin was increased (P < 0.01), protein levels of MMP-2 and MMP-9, integrin-β1 and integrin-α5 were decreased (P < 0.05), and cell invasion ability was reduced along with decreased DNMT1 and DNMT3A expression (P < 0.05). However, overexpression of DNMT1, DNMT3A and DNMT3B in HTR-8/SVneo cells promoted the up-regulation of interstitial markers N-cadherin, and MMP-2 and MMP-9 (P < 0.05). Conclusion H/R regulates the expression of EMT-related factors such as MMP-2/-9 through DNMTs, and thereby reduces the migration and invasion abilities of EVT cells.

Embryonic and fetal development can be affected during gestation by exposure to xenobiotics that cross the placenta. Liquid crystal monomers (LCMs) are emerging contaminants commonly found in indoor environments; however, whether they can cross the placenta and affect placental development remains unexplored. Here, we develop an evaluation system that integrates human biomonitoring, uterine perfusion in pregnant rats, and placental cells. We find fourteen out of the fifty-six LCMs that are detected in maternal and cord serum samples from ninety-three healthy pregnant women, at median levels of 13.9 and 18.1 ng/mL, respectively. Subsequent explorations of in utero exposure in rats indicate that aromatic amino acid transporter 1 (SLC16A10) mediates transplacental transportation of the LCMs. Placental cells exposed to LCMs exhibit delayed placental development and reduced progesterone release. These findings show that SLC16A10-mediated transplacental transportation of LCMs inhibits placental development and progesterone release, highlighting the importance of gestational exposure to emerging contaminants. Liquid crystal monomers are emerging contaminants; however, whether they can cross the placenta and affect placental development remains unexplored. Here, the authors show SLC16A10- mediated transplacental transportation of LCMs inhibits placental development and progesterone release. [ABSTRACT FROM AUTHOR]

Cell clustering is typically the initial step in single-cell RNA sequencing (scRNA-seq) analyses. The performance of clustering considerably impacts the validity and reproducibility of cell identification. A variety of clustering algorithms have been developed for scRNA-seq data. These algorithms generate cell label sets that assign each cell to a cluster. However, different algorithms usually yield different label sets, which can introduce variations in cell-type identification based on the generated label sets. Currently, the performance of these algorithms has not been systematically evaluated in single-cell transcriptome studies. Herein, we performed a critical assessment of seven state-of-the-art clustering algorithms including four deep learning-based clustering algorithms and commonly used methods Seurat, Cosine-based Tanimoto similarity-refined graph for community detection using Leiden's algorithm (CosTaL) and Single-cell consensus clustering (SC3). We used diverse evaluation indices based on 10 different scRNA-seq benchmarks to systematically evaluate their clustering performance. Our results show that CosTaL, Seurat, Deep Embedding for Single-cell Clustering (DESC) and SC3 consistently outperformed Single-Cell Clustering Assessment Framework and scDeepCluster based on nine effectiveness scores. Notably, CosTaL and DESC demonstrated superior performance in clustering specific cell types. The performance of the single-cell Variational Inference tools varied across different datasets, suggesting its sensitivity to certain dataset characteristics. Notably, DESC exhibited promising results for cell subtype identification and capturing cellular heterogeneity. In addition, SC3 requires more memory and exhibits slower computation speed compared to other algorithms for the same dataset. In sum, this study provides useful guidance for selecting appropriate clustering methods in scRNA-seq data analysis. [ABSTRACT FROM AUTHOR]

Preeclampsia is a leading contributor to increased maternal morbidity and mortality in the perinatal period. Increasing evidence demonstrates that ferroptosis is an essential mechanism for the pathogenesis of preeclampsia. Elabela is a novel small-molecule polypeptide, mainly expressed in embryonic and transplacental tissues, with an ability to promote cell proliferation and invasion. However, its specific regulatory mechanism in preeclampsia has not been completely elucidated. In this study, we first reveal an increased grade of ferroptosis accompanied by a downregulation of the expression of Elabela in preeclampsia placentas. We then confirm the presence of a ferroptosis phenotype in the placenta of the mouse PE-like model, and Elabela can reduce ferroptosis in the placenta and improve adverse pregnancy outcomes. Furthermore, we demonstrate that targeting Elabela alleviates the cellular dysfunction mediated by Erastin promoting increased lipid peroxidation in vitro. Subsequent mechanistic studies suggest that Elabela increases FTH1 levels by inhibiting the ferritinophagy pathway, and consequently chelates the intracellular labile iron pool and eventually arrests ferroptosis. In conclusion, Elabela deficiency exacerbates ferroptosis in the placenta, which is among the potential mechanisms in the pathogenesis of preeclampsia. Targeting the Elabela–ferritinophagy–ferroptosis signaling axis provides a new therapeutic intervention strategy to alleviate preeclampsia. [ABSTRACT FROM AUTHOR]