{
  "abstract": "Background: Insufficient placental angiogenesis is a predominant pathological cause of fetal growth restriction (FGR). Placental capillary development is regulated in a sex-dependent manner, with female placentas exhibiting greater susceptibility to angiogenic dysfunction than male placentas. However, the sex-specific interplay between microRNAs (miRNAs) and human placental angiogenesis in FGR pathogenesis remains poorly defined. Emerging transcriptomic sequencing evidence has implicated miR-543 as a pivotal regulator of impaired angiogenesis in female FGR placentas. This study aimed to elucidate the sex-dependent mechanistic role of miR-543 in modulating placental angiogenesis in a cell-specific manner.\n\nMethod: FGR pregnancies were recruited, and placental tissues were collected after delivery. The dual-luciferase reporter assay was used to detect the direct binding site of miR-543 to ANGPT2. Next, immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to detect the expression and localization of ANGPT2. To verify the cell-specific gene expression of miR-543 and ANGPT2, laser capture microdissection (LCM) was employed to isolate endothelial cells from human placentas. The gene expression levels of miR-543 and ANGPT2 were quantified by qRT-PCR. CCK8, wound healing, Transwell, and tube formation assays and flow cytometry were performed to assess the functional effects of miR-543 and ANGPT2 on the biological function of human umbilical vein endothelial cells (HUVECs). The PI3K/AKT/mTOR signaling pathway was predicted and verified by Western blotting.\n\nResults: Significantly downregulated miR-543 expression was observed in the placentas of female FGR fetuses relative to matched normal controls. According to target gene prediction and the dual-luciferase reporter assay, ANGTP2 was identified as a target candidate of miR-543. Moreover, immunofluorescence staining and LCM analysis verified the cell-specific distribution of ANGPT2 in female FGR placentas, partly indicating its key involvement in placental capillary angiogenesis. Furthermore, dysregulated expression of miR-543 and ANGPT2 was closely correlated with aberrant proliferation, migration, and apoptosis of HUVECs. KEGG analysis revealed that the candidate targets of miR-543 were mainly enriched in the PI3K/AKT/mTOR pathway. Western blot analysis demonstrated that the PI3K/AKT/mTOR signaling pathway mediated the ANGPT2-induced attenuation of placental angiogenesis in female FGR.\n\nConclusion: miR-543 negatively regulated ANGPT2 expression, leading to impaired endothelial cell function via inactivation of the PI3K/AKT/mTOR signaling pathway. This, in turn, contributed to sex-specific inhibition of capillary angiogenesis in the placenta of female fetuses. These findings reveal a novel miRNA-mediated, sex-dependent regulatory mechanism underlying the pathogenesis of impaired placental angiogenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Clinical Medicine Research Center, The Fourth Hospital of Shijiazhuang , , ,",
    "Department of Obstetrics, The Fourth Hospital of Shijiazhuang , , ,",
    "Department of Obstetrics, Xingtai People’s Hospital , , ,",
    "Institute of Reproductive Medicine of Shijiazhuang, The Fourth Hospital of Shijiazhuang , , ,",
    "Hebei Key Laboratory of Maternal and Fetal Medicine,The Fourth Hospital of Shijiazhuang , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wenhui Song"
    },
    {
      "affs": [
        1
      ],
      "name": "Xuemei Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Chunyan Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Yuanyuan Zhao"
    },
    {
      "affs": [
        3
      ],
      "name": "Xinxian Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Qing Guo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0th6hqceveh7f.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1912518",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719480/?tool=EBI",
  "id": "0th6hqceveh7f",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13719480",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2729|Pregnancy and preeclampsia studies"
    ]
  ],
  "openalex": "W7222715176",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719480/pdf/?tool=EBI",
  "pmcid": "PMC13719480",
  "pmid": "42964304",
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0th6hqceveh7f.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13719480",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13719480"
    },
    {
      "first_seen": "2026-11-02T12:23:26Z",
      "native_id": "PMC13719480",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1912518"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2729|Pregnancy and preeclampsia studies",
      "subfield": "reproductive-child"
    }
  ],
  "title": "miRNA-543 attenuates placental angiogenesis in female fetal growth restriction by targeting ANGPT2 and inhibiting the PI3K/AKT/mTOR pathway",
  "title_text": "miRNA-543 attenuates placental angiogenesis in female fetal growth restriction by targeting ANGPT2 and inhibiting the PI3K/AKT/mTOR pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:32Z",
  "url": "https://research.draconitic.com/paper/0th6hqceveh7f",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}