ArticleMolecular human reproduction2020
Abnormal Cullin1 neddylation-mediated p21 accumulation participates in the pathogenesis of recurrent spontaneous abortion by regulating trophoblast cell proliferation and differentiation.
Article in Molecular human reproduction, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Bisphenol B Exposure Induces Miscarriage by Suppressing Migration/Invasion and Migrasome Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genomics of pregnancy loss.Journal of assisted reproduction and genetics · 2026Review
- Dysregulation of MYBL2 impairs extravillous trophoblast lineage development and function, contributing to recurrent spontaneous abortion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibition of BCAT1 expression improves recurrent miscarriage by regulating cellular dysfunction and inflammation of trophoblasts.Cell and tissue research · 2024Article
- Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease.Open medicine (Warsaw, Poland) · 2024Article
- Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway.International journal of molecular sciences · 2023Article
- Research progress of E3 ubiquitin ligase regulating biological behavior of human placental trophoblast cells.Frontiers in endocrinology · 2023Review
- Review
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- Lnc-HZ08 regulates BPDE-induced trophoblast cell dysfunctions by promoting PI3K ubiquitin degradation and is associated with miscarriage.Cell biology and toxicology · 2022Article
- Review
- S100P promotes trophoblast syncytialization during early placenta development by regulating YAP1.Frontiers in endocrinology · 2022Article
- FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway.Molecular medicine reports · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The study explores the role of neddylation in early trophoblast development and its alteration during the pathogenesis of recurrent spontaneous abortion (RSA). Immunofluorescence and western blot were conducted to evaluate the expression pattern of NEDD8 protein in the first-trimester placentas of healthy control and RSA patients. Neddylated-cullins, especially neddylated-cullin1, were downregulated and their substrate, p21, was accumulated in RSA samples. NEDD8 cytoplasmic recruitment was observed in extravillous trophoblast (EVT) progenitors of RSA placentas. Consistent with the results of clinical samples, neddylation inhibition using MLN4924 in trophoblast cell lines caused obvious p21 accumulation and free NEDD8 cytoplasmic recruitment. Further in vitro study demonstrated neddylation inhibition attenuated proliferation of Jeg-3 cells via p21 accumulation. Moreover, when trophoblast stem (TS) cells derived from first-trimester placentas were cultured for differentiation analyses. MLN4924 impaired the differentiation of TS cells towards EVTs by downregulating HLA-G and GATA3. p21 knockdown could partly rescue MLN4924-suppressed HLA-G and GATA3 expression. In conclusion, cullin1 neddylation-mediated p21 degradation is required for trophoblast proliferation and can affect trophoblast plasticity by affecting HLA-G and GATA3 expression. The results provide insights into the pathological mechanism of RSA and the biological regulation of trophoblast development.
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