New insights into the role of oxytocin signaling in preeclampsia
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Background
Oxytocin signaling may play an important role in the human placenta during pregnancy, where abnormal function can cause pregnancy complications such as preeclampsia, a hypertension syndrome with elusive etiology, treatment, and diagnosis. As pregnancy progresses, the clinical effects of high blood pressure tend to worsen. Therefore, an early diagnosis of preeclampsia is necessary for a successful pregnancy.
Method
This study examined placenta and plasma samples from normal and preeclamptic pregnancies, approved by the Institutional Review Board. qRT-PCR, western blot, ELISA, gelatin zymography, and ChIP were performed on placental tissues. JEG-3 cells and HUVECs were cultured under normoxia or hypoxia with oxytocin or atosiban. siRNA/miRNA transfections and RUPP rat models assessed oxytocin’s effects. Data were analyzed using ANOVA and Duncan’s test (P ≤ 0.05) in SPSS.
Result
Here, we assessed the effects of oxytocin signaling on key placental functions and its correlation with preeclampsia, revealing a significant association with placental dysfunction. Our findings revealed that oxytocin increased trophoblast invasion via ERK1/2- and JNK/AP-1-dependent pathways. Notably, oxytocin signaling was inhibited by hsa-miR-193b-5p and hypoxia. Administering atosiban to pregnant rats hindered placental invasion activity, mirroring symptoms of preeclampsia, and disrupted placental development. Finally, we examined oxytocin signaling in patients with preeclampsia by analyzing oxytocin levels in the first trimester. Oxytocin levels were higher in those who later developed preeclampsia than normal pregnant women.
Conclusion
These results indicate that changes in oxytocin signaling are related with preeclampsia throughout pregnancy, emphasizing its potential as a novel early diagnostic biomarker.
