Experimental Animal Models of Preeclampsia: Mechanisms, Strengths, and Translational Relevance.

CLINICAL PROBLEM: Preeclampsia is a heterogeneous hypertensive disorder of pregnancy characterized by new-onset hypertension and end-organ dysfunction, affecting 5% to 10% of pregnancies globally. It is associated with significant maternal and fetal morbidity and mortality, and delivery remains the only definitive treatment. Understanding the underlying mechanisms is essential for the development of effective therapies.

RECOMMENDATIONS: Given the heterogeneity of preeclampsia and the absence of a single experimental model that fully recapitulates the human disease, the purpose of this review is to evaluate current animal models of preeclampsia according to the pathophysiological mechanisms they represent. We discuss the strengths, limitations, and translational relevance of these models, identify gaps in the existing experimental framework, and highlight opportunities for future model development and therapeutic discovery.

SUMMARY: Current models reproduce distinct features of preeclampsia, including abnormal placentation, placental ischemia, angiogenic imbalance, endothelial dysfunction, immune activation, and metabolic dysregulation. Despite mechanistic insights, translational success has been limited. Future progress will depend on mechanism-driven model selections, development of models that better capture early placentation defects and disease heterogeneity, multi-hit approaches, including the incorporation of maternal comorbidities, and integration of human-relevant experimental systems to improve clinical translation.