Pathophysiology of Preeclampsia and Intrauterine Growth Restriction

Preeclampsia and intrauterine growth restriction (IUGR) are major pregnancy complications characterised by placental dysfunction that affect maternal and fetal health worldwide. Both conditions originate from abnormal maternal spiral artery remodelling by extravillous trophoblasts, leading to placental hypoperfusion, intermittent hypoxia and oxidative injury. In preeclampsia, the compromised placenta releases anti-angiogenic factors, pro-inflammatory cytokines and trophoblastic debris into the maternal circulation, precipitating systemic endothelial dysfunction, hypertension, proteinuria and end-organ damage. In IUGR, impaired placental transport of oxygen and nutrients restricts fetal growth, resulting in perinatal morbidity and long-term cardio-metabolic sequelae. Underlying molecular mechanisms include endoplasmic reticulum stress, defective autophagy, proteinopathy and aberrant cell death pathways. Genetic and environmental factors modulate disease severity and timing of onset. Advances in understanding key molecular drivers are guiding the development of novel biomarkers and targeted interventions to improve outcomes across diverse healthcare settings.

Research from Nature Portfolio

Recent studies have revealed cis P-tau as a central circulating and placental driver of preeclampsia. Elevated cis P-tau accumulates in hypoxic trophoblasts and in the serum of affected patients due to Pin1 inactivation. Depletion of cis P-tau from patient serum restores trophoblast invasion and endovascular activity and prevents preeclampsia-like clinical features in humanised mouse models. This discovery positions cis P-tau as both an early biomarker and a therapeutic target through stereo-specific antibody intervention, with promising prospects for clinical translation.

Pathophysiology of Preeclampsia and Intrauterine Growth Restriction publication trend

The graph below shows the total number of articles in pathophysiology of preeclampsia and intrauterine growth restriction across all publications each year (not limited to Nature Index journals).

Technical terms

Spiral artery remodelling: Transformation of maternal uterine arteries by trophoblast invasion to increase placental blood flow.

Trophoblast: Fetal-derived placental cells that invade the maternal decidua to establish nutrient and gas exchange.

Endoplasmic reticulum stress: Cellular response to accumulation of unfolded proteins, activating adaptive signalling or apoptosis.

Oxidative stress: Imbalance between reactive oxygen species and antioxidant defences, leading to cellular damage.

Autophagy: Lysosome-mediated degradation of damaged cellular components to maintain homeostasis.

Necroptosis: Regulated form of necrosis involving receptor-interacting kinases and release of inflammatory mediators.

cis P-tau: Pathological conformation of tau protein implicated in placental and circulatory dysfunction in preeclampsia.

References

1. Cis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia. Nature Communications (2023).
2. Exploiting sweet relief for preeclampsia by targeting autophagy-lysosomal machinery and proteinopathy. Experimental & Molecular Medicine (2024).
3. Thrombospondin‐1 Regulates Trophoblast Necroptosis via NEDD4‐Mediated Ubiquitination of TAK1 in Preeclampsia. Advanced Science (2024).
4. Placental Endoplasmic Reticulum Stress and Oxidative Stress in the Pathophysiology of Unexplained Intrauterine Growth Restriction and Early Onset Preeclampsia. Placenta (2008).