ArticleReproductive sciences (Thousand Oaks, Calif.)2022
Fragile X-Related Protein 1 (FXR1) Promotes Trophoblast Migration at Early Pregnancy via Downregulation of GDF-15 Expression.
Article in Reproductive sciences (Thousand Oaks, Calif.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 28 citations in OpenAlex.
- The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy.Human reproduction update · 2024Review
- MiR-3074-5p Regulates Trophoblasts Function via EIF2S1/GDF15 Pathway in Recurrent Miscarriage.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders.medRxiv : the preprint server for health sciences · 2023Article
- Exosomal circZNF451 restrains anti-PD1 treatment in lung adenocarcinoma via polarizing macrophages by complexing with TRIM56 and FXR1.Journal of experimental & clinical cancer research : CR · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
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Abstract
Fragile X-related protein 1 (FXR1) is an RNA-binding protein that can regulate specific mRNA decay in cells. Our previous study showed that FXR1 expression was significantly decreased in trophoblasts from patients with unexplained recurrent spontaneous abortion (RSA); however, the role of FXR1 in trophoblast function during early placenta development has not been fully elucidated. In this study, we found that knockdown of FXR1 using siRNA effectively inhibited the migration of HTR-8 cells and extravillous trophoblast (EVT) outgrowth in an ex vivo extravillous explant culture model. Furthermore, through analysis of a panel of cytokines, we found that the GDF-15 protein was upregulated after knockdown of FXR1 in HTR-8/SVneo cells. This was further confirmed by western blotting and immunofluorescence in HTR-8/SVneo cells and an extravillous explant. Our data also showed that FXR1 expression was downregulated and GDF-15 was upregulated in chorionic villous tissues from RSA patients compared with those from healthy controls (HCs). Further, immunohistochemistry showed a strong expression of GDF-15 in chorionic villous tissue in the RSA group, which was mainly distributed in villous trophoblasts (CTBs) and syncytiotrophoblasts (STBs). Moreover, knockdown of GDF-15 enhanced the migration of HTR-8 cells, while overexpression of GDF-15 using plasmid or treatment with recombinant human GDF-15 protein inhibited trophoblast migration. Importantly, RNA-binding protein immunoprecipitation showed that FXR1 directly bound to the 3'-UTR of GDF-15 mRNA to promote GDF-15 mRNA decay. Together, our data provide new insight into the function of FXR1 in human placenta via regulation of GDF-15 expression in trophoblasts and suggest a possible pathological process involved in RSA.
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