Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitus

Abstract 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...

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Main Authors: Zhuo Chen, Li Yang, Li Geng, Xinwen Zhang, Mingyu Du, Yonghu Sun, Lin Zhao, Bing Bai, Xiaohong Li
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-04836-1
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author Zhuo Chen
Li Yang
Li Geng
Xinwen Zhang
Mingyu Du
Yonghu Sun
Lin Zhao
Bing Bai
Xiaohong Li
author_facet Zhuo Chen
Li Yang
Li Geng
Xinwen Zhang
Mingyu Du
Yonghu Sun
Lin Zhao
Bing Bai
Xiaohong Li
author_sort Zhuo Chen
collection DOAJ
description Abstract 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.
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spelling doaj-art-e7c637e124ba41cca0b334f3f21533ff2025-08-20T02:05:38ZengNature PortfolioScientific Reports2045-23222025-06-0115111710.1038/s41598-025-04836-1Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitusZhuo Chen0Li Yang1Li Geng2Xinwen Zhang3Mingyu Du4Yonghu Sun5Lin Zhao6Bing Bai7Xiaohong Li8Department of Obstetrics, the First Affiliated Hospital of Kunming Medical UniversitySchool of Basic Medicine, Kunming Medical UniversityDepartment of Obstetrics, the First Affiliated Hospital of Kunming Medical UniversityDepartment of Obstetrics, the First Affiliated Hospital of Kunming Medical UniversityDepartment of Obstetrics, the First Affiliated Hospital of Kunming Medical UniversityDepartment of Obstetrics, the First Affiliated Hospital of Kunming Medical UniversityDepartment of Obstetrics, the First Affiliated Hospital of Kunming Medical UniversityDepartment of Obstetrics, the First Affiliated Hospital of Kunming Medical UniversityDepartment of Obstetrics, the First Affiliated Hospital of Kunming Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-025-04836-1PreeclampsiaWhole transcriptome analysisImmuneCompeting endogenous RNA
spellingShingle Zhuo Chen
Li Yang
Li Geng
Xinwen Zhang
Mingyu Du
Yonghu Sun
Lin Zhao
Bing Bai
Xiaohong Li
Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitus
Scientific Reports
Preeclampsia
Whole transcriptome analysis
Immune
Competing endogenous RNA
title Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitus
title_full Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitus
title_fullStr Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitus
title_full_unstemmed Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitus
title_short Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitus
title_sort placental whole transcriptome expression profile in patients with early onset late onset preeclampsia and gestational diabetes mellitus
topic Preeclampsia
Whole transcriptome analysis
Immune
Competing endogenous RNA
url https://doi.org/10.1038/s41598-025-04836-1
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