ArticleJournal of translational medicine2024
KLF4 regulates trophoblast function and associates with unexplained recurrent spontaneous abortion.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- ESRRG downregulation in early spontaneous abortion induces mitochondrial damage, leading to impaired trophoblast function.Annals of medicine · 2026Article
- Mechanism of Shoutai Wan against recurrent spontaneous abortion: regulation of decidual vascular remodeling via ERβ-ANGPT2 signaling axis.Functional & integrative genomics · 2026Article
- METTL3-Mediated m6A Modification of ACTR2 Promotes Trophoblast Cell Growth, Migration and Invasion in Unexplained Recurrent Spontaneous Abortion.Cell biochemistry and biophysics · 2026Article
- The Impact of First-Trimester Vaginal Microecology on Spontaneous Abortion: A Retrospective Cohort Study.Pathogens (Basel, Switzerland) · 2026Article
- The diagnostic value and molecular mechanism of miR-199a-5p in recurrent spontaneous abortion.Journal of assisted reproduction and genetics · 2026Article
- miR-146a/b-5p-IRAK1-NF-κB Axis Regulates Unexplained Recurrent Spontaneous Abortion.Journal of molecular recognition : JMR · 2026Article
- Lycium barbarum polysaccharide inhibits Hcy-induced vascular smooth muscle cells migration and invasion via upregulation of KLF4.Scientific reports · 2026Article
- The research on the relationship between mesenchymal stromal cell exosomes and recurrent spontaneous abortion.Archives of gynecology and obstetrics · 2026Review
- Discovery and validation of key genes and potential mechanisms linked to endothelial cell senescence and carbohydrate metabolism in recurrent spontaneous abortion.Open medicine (Warsaw, Poland) · 2026Article
- Exploring the epigenetic mechanisms of recurrent pregnancy loss: from genetic predisposition to environmental influences.Journal of assisted reproduction and genetics · 2025Review
- A comprehensive review of histone modifications during mammalian oogenesis and early embryo development.Histochemistry and cell biology · 2025Review
- MT1/cAMP/PKA Pathway in Melatonin-Regulated Sperm Capacitation.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- KLF4 orchestrates a Ccl2+ fibroblast-mediated inflammatory network driving preterm birth.Frontiers in medicine · 2025Article
- Potential common mechanisms between primary Sjögren's syndrome and Hashimoto's thyroiditis: a public databases-based study.Frontiers in genetics · 2025Article
- Analysis of complex chromosomal structural variants through optical genome mapping integrated with karyotyping.Frontiers in genetics · 2025Article
- BRD4 Inhibitor Alleviates Recurrent Spontaneous Abortion via Regulating BRD4/STAT3/IL-17A Axis to Decrease the Th17 Cell Differentiation.Reproductive medicine and biologyArticle
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Authors and funding
8 authors.
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Abstract
backgroundRecurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions before 20 weeks with the same spouse [1]. However, approximately 50% of RSA cases of unknown cause are classified as unexplained recurrent spontaneous abortion (URSA). Potential factors include decreased trophoblast cell migration and invasion, leading to impaired placental implantation and maintenance of the normal maternal-fetal interface. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the potential role and mechanism of KLF4 in regulating URSA by influencing the invasion and migration ability of trophoblast cells.
methodsWe firstly identified 817 differentially expressed genes by performing a difference analysis of the dataset GSE121950 [2] related to recurrent abortion, and intersected the top 10 genes obtained respectively by the three algorithms: DMNC, MNC, and EPC using Venn Diagram.To detect the expression levels of core genes, villi samples were obtained from normal pregnant women and patients with URSA. RT-qPCR analysis revealed a significant difference in KLF4 mRNA expression and KLF4 was then analyzed. Trophoblast cell lines HTR8 and JEG3 were used to investigate the effect of KLF4 on trophoblastic function. Wound healing and transwell assays was performed to detect the invasion and migration of trophoblast cells. The expression of epithelial-mesenchymal transition(EMT) molecules were detected by RT-qPCR and western blot. Promoter detection and epigenetic modification were detected by chromatin immunoprecipitation (ChIP) assay. Molecular nuclear localization was detected by immunofluorescence and subcellular fractionation. Miscarried mice model was used to study the effects of KLF4 on URSA induced by reduced trophoblast invasion and migration.
resultsKLF4 is highly expressed in the villi of patients with URSA. KLF4 inhibits the expression level of H3R2ME2a in trophoblast cells by regulating the transcriptional level and nuclear translocation of PRMT6, thereby inhibiting the possible regulatory mechanism of trophoblastic invasion and providing a potential treatment strategy for URSA in vivo.
conclusionsThe KLF4/PRMT6/H3R2ME2a axis regulates mechanisms associated with unexplained recurrent spontaneous abortion by regulating trophoblast function.
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