Altered Notch pathway-related protein expression in cord blood of preeclampsia offspring: a pilot study

This study aimed to test the hypothesis that the NCOR2/DLL-4/Jagged-1 axis is dysregulated in cord blood of offspring from mothers with preeclampsia (PE) and gestational hypertension (GH), favoring an anti-angiogenic profile. We compared expression levels of these Notch pathway components among PE, GH, and healthy control groups to explore their potential role in fetal vascular programming. This is a prospective cohort study, including 17 mother-offspring pairs with gestational hypertension, 17 mother-offspring pairs with preeclampsia, and 34 healthy mother-offspring pairs as controls. Standardized questionnaires were used to collect family and birth information, medical records were used to collect clinical data, and Western blot was employed to measure the expression levels of NCOR2, DLL-4, and Jagged-1 in cord blood. We analyzed the differences in offspring cord blood proteins among the three groups. Cord blood protein expression revealed significant dysregulation of the NCOR2/DLL-4/Jagged-1 axis. Compared to the control group (1.36 ± 0.44), the GH (1.00 ± 0.12) and PE (0.94 ± 0.15) groups were characterized by a significant downregulation of NCOR2 (p = 0.001). Furthermore, a progressive and significant increase in DLL-4 (p = 0.001) was observed across the control (0.82 ± 0.28), GH (0.98 ± 0.17), and PE (1.27 ± 0.40) groups, which was accompanied by a significant stepwise decrease in Jagged-1 expression (control: 1.36 ± 0.28, GH: 1.02 ± 0.12, PE: 0.87 ± 0.18, p < 0.001). The cord blood levels of NCOR2 and Jagged-1 proteins were significantly decreased in offspring of PE and GH, while DLL-4 protein expression was significantly increased in offspring of PE. These findings suggest that dysregulated Notch signaling, characterized by an anti-angiogenic profile in the fetal circulation, may contribute to the vascular programming observed in offspring of preeclamptic pregnancies.