Improvement in Clinical Features of L-NAME-Induced Preeclampsia-like Rats through Reduced SERPINA5 Expression

Abstract

Pre-eclampsia (PE) is a severe pregnancy disorder that poses a significant health risk to both mother and fetus, with no preventive or therapeutic measures. Our previous research suggested an association between elevated SERPINA5 levels and PE features. This study investigated whether SERPINA5 could be a potential therapeutic target for PE. We established PE-like features in pregnant rats using L-NAME (75 mg/kg/d) treatment. Adenoviruses carrying overexpressed or suppressed SERPINA5 genes were intravenously injected into these PE rats on the fifth and seventh days of pregnancy. We evaluated the rats’ systolic blood pressure, urine protein concentration, and placental and fetal metrics and histology. Placental gene expression following SERPINA5 overexpression was evaluated using mRNA sequencing. The L-NAME-induced PE rat model observed a significant increase in placental and peripheral SERPINA5 levels. The overexpression of SERPINA5 exacerbated L-NAME-induced hypertension and proteinuria in pregnant rats. A histology examination revealed a smaller placental junctional zone in L-NAME + overexpressing rats. Placental gene expression analysis in the L-NAME + overexpressing group indicated increased coagulation activation. L-NAME-induced hypertension and proteinuria were mitigated when SERPINA5 expression was suppressed. Additionally, placental development was improved in the SERPINA5-suppressed group. Our findings suggested that SERPINA5 may worsen L-NAME-induced PE-like features by promoting the activation of the coagulation cascade. Therefore, reducing SERPINA5 expression could potentially serve as a therapeutic strategy for PE.