Ghrelin attenuates preeclampsia-like features by reprogramming decidual macrophages and improving placental remodeling

Preeclampsia (PE) is a severe, pregnancy-specific hypertensive disorder affecting 2–8% of pregnancies, leading to significant maternal and fetal morbidity and mortality, including fetal growth restriction (FGR) and preterm birth. Current treatments are limited, with delivery being the only definitive cure. The pathogenesis involves defective trophoblast invasion and insufficient spiral artery remodeling, leading to placental ischemia and the release of factors like soluble fms-like tyrosine kinase-1 (sFlt-1), which impairs vascular function. A key pathological feature is immune microenvironment dysregulation at the maternal-fetal interface, particularly an imbalance in decidual macrophage phenotypes, highlighting an urgent need for targeted interventions.

Researchers investigated the role of the Ghrelin/GHSR-1a axis in preeclampsia (PE) using both clinical analysis of human decidual tissues and an animal model of PE. Clinical analysis assessed the endogenous Ghrelin/GHSR-1a axis in PE decidual tissues. In the animal model, exogenous Ghrelin was administered to evaluate its impact on PE-like features, decidual macrophage phenotypes, and placental remodeling. The study aimed to clarify how Ghrelin influences the immune microenvironment and placental health to mitigate PE pathology. Specific doses, routes, and frequencies for the animal model were not detailed in the provided abstract.

Clinical analysis of PE decidual tissues revealed a severity-dependent compensatory escalation of the endogenous Ghrelin/GHSR-1a axis, suggesting an intrinsic protective response to pregnancy-associated pathological stress. In the animal model, exogenous Ghrelin supplementation effectively attenuated preeclampsia-like features. This included significant improvements in maternal hypertension and proteinuria, key clinical markers of PE. Ghrelin achieved these effects by actively reprogramming decidual macrophages, shifting their phenotype to a more favorable profile for pregnancy. Furthermore, the intervention led to improved placental remodeling, addressing a critical defect in PE pathogenesis. This suggests Ghrelin directly targets the underlying immune and vascular dysfunctions. The study highlights the Ghrelin/GHSR-1a axis as a crucial regulator of the maternal-fetal interface.

The Ghrelin/GHSR-1a axis attenuates preeclampsia-like features through decidual macrophage reprogramming and improved placental remodeling.