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.