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Objective: Preeclampsia (PE) is a maternal multisystem disease with an unclear mechanism. Data showed that MiR-95-3p promoted cell migration, invasion and proliferation, leading to the occurrence and development of many cancers, and placental trophoblasts and tumor cells had similar migration, invasion and proliferation abilities. Meanwhile we found that MiR-95-3p was differentially expressed in PE and normal placenta. Therefore, this article aimed to explore the biological function and mechanism of miR-95-3p in PE., Methods: The expression of miR-95-3p in PE and normal placental tissue was explored by high-throughput sequencing and qRT-PCR. The effects of miR-95-3p on trophoblast migration, invasion, proliferation, angiogenesis and apoptosis were investigated by Transwell migration and invasion assays, cell viability assay, tube formation assay and flow cytometry in two trophoblast cell lines (HTR-8/SVneo and JAR). The miR-95-3p target gene EPM2A was identified and verified by unique identifier mRNA next-generation sequencing and dual-luciferase reporter gene experiments. Rescue experiments were conducted to investigate whether miR-95-3p regulated EPM2A to participate in trophoblast migration and invasion. Finally, the effects of miR-95-3p and EPM2A on the expression of angiogenic factors and inflammation-related factors were investigated by ELISA., Results: We found that miR-95-3p was expressed at low levels in the placental tissue of patients with PE and was negatively correlated with EPM2A expression. In vitro upregulation of miR-95-3p and downregulation of EPM2A promote trophoblast migration, invasion and proliferation. Furthermore, EPM2A was confirmed as a target mRNA of miR-95-3p. Upregulation of EPM2A mitigated miR-95-3p-mediated promotion of trophoblast migration and invasion and vice versa. Finally, both miR-95-3p and EPM2A regulate the expression of trophoblast angiogenesis-related factors and inflammation-related factors., Conclusion: Our findings demonstrated that miR-95-3p promoted the migration and invasion of trophoblast cells by targeting EPM2A to inhibit the occurrence and development of PE., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Increasing evidence suggests that RNA m5C modification and its regulators have been confirmed to be associated with the pathogenesis of many diseases. However, the distribution and biological functions of m5C in mRNAs of placental tissues remain unknown. we collected placentae from normotensive pregnancies (CTR) and preeclampsia patients (PE) to analyze the transcriptomic profiling of m5C RNA methylation through m5C RNA immunoprecipitation (UMI-MeRIP-Seq). we discovered that overall m5C methylation peaks were decreased in placental tissues from PE patients. And, 2844 aberrant m5C peaks were identified, of which respectively 1304 m5C peaks were upregulated and 1540 peaks were downregulated. The distribution of m5C peaks were mainly located in CDS (coding sequences) regions in placental tissues of both groups, but compared with the CTR group, the m5C peak in PE group before the stop code of CDS was significantly increased and even higher than the peak value after start code in CDS. Differentially methylated genes were mainly enriched in MAPK/cAMP signaling pathway. Moreover, the up-regulated genes with hypermethylated modification were enriched in the processes of hypoxia, inflammation/immune response. Finally, through analyzing the mRNA expression levels of m5C RNA methylation regulators, we found only DNMT3B and TET3 were significantly upregulated in PE samples than in control group. And they are not only negatively correlated with each other, but also closely related to those differentially expressed genes modified by differential methylation.Our findings provide new insights regarding alterations of m5C RNA modification into the pathogenic mechanisms of PE., (© 2023 Federation of American Societies for Experimental Biology.)

Background: Preeclampsia is a pregnancy syndrome that may utilize multiple pathogenic mechanisms. Insufficient trophoblast invasion and impaired uterine spiral artery remodeling are believed to be the pathological basis; yet the underlying mechanisms remain largely unclear., Methods: The placental BCAM (basal cell adhesion molecule) expression and important clinical indicators were detected and correlation analysis was performed. MiRNAs directly targeting BCAM were predicted and further verified by dual-luciferase reporter gene, and the downstream molecular mechanisms of BCAM were investigated in both HTR-8/SVneo and JAR cells. In addition, pregnant/nonpregnant rats were treated with adenoviruses containing BCAM shRNA genes (Ad-shBCAM) on gestational 9.5 days to detect the preeclamptic features., Results: The BCAM is highly expressed on the trophoblast membrane and decreased in the preeclamptic placentae. In HTR-8/SVneo and JAR cells, BCAM knockdown inhibited trophoblast proliferation, migration, and invasion, and suppressed phosphorylation on Y705 of STAT3 dependent on the downregulation of PIK3R6. Moreover, miR-199a-5p mediated the degradation of BCAM and also inhibited trophoblast proliferation, migration, and invasion. In vivo, BCAM deficiency induced a preeclampsia-like phenotype included elevated systolic blood pressure, proteinuria, impaired morphology and function of multiple organs (placenta, liver, and kidney), and fetal growth restriction. The expression of placenta BCAM/PIK3R6/p-STAT3 signaling was also downregulated in this preeclampsia rat model., Conclusions: MiR-199a-5p mediated-BCAM deficiency contributes to the suppression of trophoblast proliferation, migration, and invasion by inhibiting PIK3R6/p-STAT3 signaling, which may lead to poor placentation and result in preeclampsia-like phenotypes. Our study provides a new academic perspective on the pathogenesis of preeclampsia.

Background: The widely accepted explanation of preeclampsia (PE) pathogenesis is insufficient trophoblast invasion and impaired uterine spiral artery remodeling. However, the underlying molecular mechanism remains unclear., Methods: We performed transcriptome sequencing on placentas of normal and PE patients and identified 976 differentially expressed long noncoding RNAs (lncRNAs). TCF21 antisense RNA inducing demethylation (TARID) was one of the most significantly differentially expressed lncRNAs and was negatively correlated with the systolic and diastolic blood pressure in PE patients. Furthermore, we verified the effect of TARID on the biological behavior of trophoblasts and performed UID mRNA-seq to identify the effectors downstream of TARID. Then, co-transfection experiments were used to better illustrate the interaction between TARID and its downstream effector., Results: We concluded that the downregulation of TARID expression may inhibit trophoblast infiltration and spiral artery remodeling through inhibition of cell migration, invasion, and tube formation mediated through the CXCL3/ERK/MAPK pathway., Conclusions: Overall, these findings suggested that TARID may be a therapeutic target for PE through the CXCL3/ERK/MAPK pathway., (© 2022. The Author(s).)

Converging lines of evidence suggest an association between schizophrenia and prenatal neurodevelopmental disorders. Preeclampsia is a multisystem disease based on the coexistence of pregnancy and elevated blood pressure, which increases the risk for offspring abnormal neurodevelopment. Previous studies have showed maternal preeclampsia is associated with an increased risk of offspring schizophrenia, but the molecular mechanism remains unclear. In this study, we sought to identify key protein-coding genes between maternal preeclampsia and offspring schizophrenia. GSE53987 and GSE166846 datasets from Gene Expression Omnibus (GEO) database were analysed to obtain common differentially expressed genes (DEGs) between preeclampsia and schizophrenia. GSE62105 dataset was analysed to identify the DEGs' expressions in neural cells from one control and one schizophrenic patient. GSE92845 dataset was analysed to describe the changes of the DEGs in human neural stem cells. In total, we obtained ten common DEGs. All of them expressed differently in neural cells of the control and schizophrenic patient. We chose the six DEGs that had similar trend in both neural cells and UCB from preeclampsia patients and analysed their expressions in human neural stem cells over time. We found the expressions of CKAP5 and SAT1 in day 30 had significant difference comparing with those in day 0. The KEGG pathway analysis of their interaction proteins showed they were involved with metabolism. Our results may provide a new insight for genetic basis of relationship between maternal preeclampsia and offspring schizophrenia., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)