Role of Progesterone Membrane Receptors in the Pathogenesis of Preeclampsia

Overview

Preeclampsia is a pregnancy-specific hypertensive disorder and remains a leading cause of maternal and perinatal morbidity and mortality worldwide. Although abnormal placentation, impaired trophoblast invasion, endothelial dysfunction, and immune dysregulation have been implicated in its pathogenesis, the underlying molecular mechanisms are not fully understood. Progesterone plays a critical role in the maintenance of pregnancy through both classical nuclear receptors and membrane-associated progesterone receptors. Emerging evidence suggests that progesterone membrane receptors, including progesterone receptor membrane component 1 (PGRMC1), progesterone receptor membrane component 2 (PGRMC2), and members of the progestin and adipoQ receptor (PAQR) family, may regulate trophoblast invasion, placental development, and inflammatory responses. This study aims to compare the placental expression levels of PGRMC1, PGRMC2, and PAQR family receptors between women with preeclampsia and healthy pregnant controls and to investigate their potential role in the pathophysiology of preeclampsia.

Preeclampsia affects approximately 3-8% of pregnancies and is characterized by new-onset hypertension and multisystem involvement after 20 weeks of gestation. Despite extensive research, its molecular pathogenesis remains incompletely understood. Progesterone is essential for successful pregnancy maintenance and contributes to uterine quiescence, trophoblast function, and maternal-fetal immune tolerance. In addition to classical genomic signaling pathways, progesterone exerts rapid non-genomic effects through membrane-associated receptors, including PGRMC1, PGRMC2, and PAQR family members. Recent studies have demonstrated that these receptors are involved in trophoblast invasion, angiogenesis, endothelial function, and inflammatory regulation. Alterations in their expression may contribute to abnormal placentation and endothelial dysfunction observed in preeclampsia. The present study will evaluate placental expression levels of PGRMC1, PGRMC2, and selected PAQR family receptors in women with preeclampsia and healthy controls. Placental tissue obtained after delivery will undergo immunohistochemical and mRNA expression analyses. The findings may improve understanding of the molecular mechanisms underlying preeclampsia and identify potential biomarkers or therapeutic targets.