Notch signaling pathway regulates the progression of fetal growth restriction through mediating immune dysfunction.

Fetal growth restriction (FGR) is associated with an increased risk of neonatal morbidity and mortality, as well as the development of metabolic syndrome in adulthood. The present study investigated the regulatory mechanisms of Notch signaling in FGR progression. The expression levels of Notch1 and Jagged1 were determined using reverse transcription-quantitative PCR, western blotting, immunofluorescence staining and immunohistochemistry (IHC). ELISA was used to measure the concentrations of IL-10, IL-17 and IL-35 in serum and placental samples. ELISA and western blotting determined the inflammation- and angiogenesis-related cytokine levels. Th17, Treg and macrophage levels were determined using IHC and flow cytometry. Additionally, hematoxylin & eosin staining and TUNEL assay assessed placenta histology and trophoblast cell apoptosis. Significant trophoblast apoptosis was observed in the placenta of FGR pregnancies. The expression of Notch1 and Jagged1 in peripheral blood mononuclear cells and placental tissues of FGR pregnancies was significantly lower than in the control group. The FGR group exhibited a remarkable inflammation, anti-angiogenesis and immune dysfunction. In conclusion, the Notch signaling pathway mediates immune balance to regulate the development of FGR. These findings offer the potential for advancing innovative predictive, diagnostic and therapeutic approaches for FGR.