Inhibition of autophagy via 3-methyladenine alleviated the progression of preeclampsia

Autophagy is a cellular mechanism for self-renewal that involves the breakdown of cytoplasmic proteins or organelles within lysosomes. Although preeclampsia (PE) exhibits several characteristics that could imply disrupted autophagy, there is limited evidence supporting the notion that impaired placental autophagy directly causes PE, as indicated by differential expression profiling of whole placental tissue. In our study, we aimed to explore the significance of autophagy in maintaining pregnancy and its association with PE. First, the RNA-seq results showed that 218 genes were differentially expressed in placentas from preeclamptic pregnancies. Notably, KEGG pathway analysis revealed significant enrichment of genes related to autophagy-related signalling pathways, including the PI3K-Akt signalling pathway, the AMPK signalling pathway, and the mTOR signalling pathway. Additionally, our findings indicate an increase in autophagy in placentas from pregnancies complicated by preeclampsia as well as in trophoblasts subjected to hypoxic conditions. Next, we examined the impact of 3-methyladenine (3-MA), a targeted inhibitor of autophagy, on the progression of PE. The administration of 3-MA profoundly alleviated the severity of PE-like symptoms in rats subjected to reduced uterine perfusion pressure (RUPP). These findings from our study suggest that inhibiting autophagy may serve as a promising approach for adjuvant chemotherapy for PE.