Preeclampsia Mechanisms and Animal Models

Preeclampsia is a pregnancy-specific multisystem disorder characterised by new-onset hypertension and proteinuria or end-organ dysfunction after 20 weeks of gestation. Central to its pathogenesis is abnormal placentation leading to impaired spiral artery remodelling, placental ischaemia and oxidative stress. These events trigger an angiogenic imbalance, with elevated anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 and reduced pro-angiogenic mediators including placental growth factor. Endothelial dysfunction ensues, manifesting as proteinuria, endotheliosis and systemic hypertension, ultimately risking maternal morbidity and adverse fetal outcomes. Animal models remain indispensable owing to ethical constraints in human studies. Surgical approaches, notably the reduced uteroplacental perfusion (RUPP) model and its selective refinement, replicate placental hypoperfusion and key biochemical features. Genetic models, such as hypertensive and obesity-prone mouse strains, allow exploration of maternal predisposition and comorbidity-driven mechanisms. Pharmacological inhibition of nitric oxide synthase or administration of anti-angiogenic agents also induce preeclamptic-like symptoms, facilitating preclinical testing. Each model captures discrete elements of preeclampsia, but no single paradigm fully mirrors the heterogeneity of human disease. Combining models and aligning them with specific pathogenic pathways enhances translational relevance and informs the development of predictive markers and novel interventions.

Research from Nature Portfolio

Refinements to the classical uteroplacental ischaemia model have focused on selective arterial clipping to induce preeclamptic features without systemic limb ischaemia. Introduced in rats, this selective reduced uteroplacental perfusion (sRUPP) approach targets uterine and ovarian arteries while sparing the lower aorta. The protocol yields elevated mean arterial pressure, heightened vascular oxidative stress and an angiogenic profile marked by increased inflammatory mediators and reduced pro-angiogenic factors. Importantly, vascular compliance remains intact, underscoring the model’s specificity for placental pathology. By avoiding peripheral ischaemia, this method offers a more precise platform for dissecting placental contributions to endothelial dysfunction and for evaluating targeted therapeutics.

Preeclampsia Mechanisms and Animal Models publication trend

The graph below shows the total number of articles in preeclampsia mechanisms and animal models across all publications each year (not limited to Nature Index journals).

Technical terms

Preeclampsia: Pregnancy-specific disorder characterised by new-onset hypertension and proteinuria or end-organ dysfunction after 20 weeks gestation.

Reduced uteroplacental perfusion (RUPP): Experimental procedure involving partial occlusion of uterine blood flow to mimic placental ischaemia.

Selective RUPP (sRUPP): A refinement of the RUPP model targeting uterine and ovarian arteries while preserving systemic perfusion.

Proteinuria: Excessive protein excretion in urine, indicating glomerular endothelial dysfunction.

Endotheliosis: Swelling of glomerular endothelial cells, a histological hallmark of renal involvement in preeclampsia.

Angiogenic imbalance: Disproportion between anti-angiogenic and pro-angiogenic factors, disrupting vascular development in the placenta.

References

1. The Clinical Value of Rodent Models in Understanding Preeclampsia Development and Progression. Current Hypertension Reports (2023).
2. Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice. PLOS ONE (2016).
3. Characterisation of the Selective Reduced Uteroplacental Perfusion (sRUPP) Model of Preeclampsia. Scientific Reports (2019).
4. Mouse models of preeclampsia with preexisting comorbidities. Frontiers in Physiology (2023).
5. Reversal of maternal obesity attenuates hypoxia and improves placental development in the preeclamptic-like BPH/5 mouse model. Biocell (2023).