Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Diabetes, Gestational*/genetics , Diabetes, Gestational*/metabolism , Diabetes, Gestational*/pathology , Diabetes, Gestational*/immunology , Pre-Eclampsia*/genetics , Pre-Eclampsia*/metabolism , Pre-Eclampsia*/pathology , Placenta*/metabolism , Transcriptome*, Humans ; Female ; Pregnancy ; Adult ; Gene Expression Profiling ; Signal Transduction

Competing Interests: Declaration. Competing interests: The authors declare no competing interests. Ethics approval: This study was approved and supervised by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University (kmmu2021670), in accordance with relevant human research ethics guidelines. The informed consent was obtained from all participants.
Preeclampsia (PE) and gestational diabetes mellitus (GDM) are significant pregnancy complications with complex pathogenesis. Therefore, we conducted a comprehensive investigation using whole-transcriptome sequencing of placental samples. The results revealed dysregulation of key pathways in early-onset-PE (OE-PE), including Wnt signaling, PI3K-Akt signaling, MAPK signaling, FoxO signaling, and TNF signaling, along with downregulation of genes related to Ca2 + conduction and hormone pathways. In late-onset-PE (LO-PE) and GDM, abnormalities were observed in immune pathways including chemokine signaling pathway and IL-17 signaling pathway, with differing immune cell infiltration patterns. EO-PE was associated with reduced T cells and B cells, while LO-PE had increased plasmacytoid dendritic and CD56bright natural killer cells. In GDM, a notable increase in the infiltration of various immune cells- including central memory CD8 T cells, monocytes, B cells, T cells, and central memory CD4 T cells - was observed. Additionally, downregulation of HLA-A and HLA-F, particularly in EO-PE, suggests immune dysregulation. CCL26-has-miR-618-has-circ-0001776 could potentially contribute to the progression of EO-PE, while CREB1-has-miR-373-3p-has-circ-0003793/has-circ-0001146 may be implicated in the LO-PE development. Additionally, GZMB-has-miR-199a-5p/has-miR-199b-5p-has-circ-0008959/novel-circ_0008792 may mediate the disease progression of GDM. In summary, genes related to placental cell functions are inhibited in PE, while autoimmune abnormalities may play a role in LO-PE and GDM pathogenesis.
(© 2025. The Author(s).)