Distinct TYRO3 and PROS1 expression levels contribute to preeclampsia pathogenesis.

Abstract

Preeclampsia (PE) is a severe placental complication occurring after the 20th week of pregnancy. PE is associated with inflammation and an increased immune reaction against the fetus. TYRO3 and PROS1 suppress inflammation by clearing apoptotic cells. Disruptions in TYRO3/PROS1 signaling may increase the risk of PE. This study investigated the role of TYRO3/PROS1 signaling in the development of PE using healthy placentae (HP) and preeclamptic placentae (PP) of six pregnant women each. Tissue morphology using hematoxylin and eosin (H&E), TYRO3, MERTK, PROS1, and GAS6 mRNA levels using qPCR and localization and expression levels of TYRO3 and PROS1 using immunohistochemical staining (IHC) were evaluated. The study results show that the levels of TYRO3, MERTK, PROS1 and GAS6 mRNA, as well as TYRO3 protein, increased in PE. TYRO3 expression was observed in extravillous trophoblast (EVTs) and syncytiotrophoblast cells (SCTs). PROS1 was observed in HP fetal vessels through IHC while absent in PP. The reduced presence of PROS1 in the cytotrophoblast layer in PE may indicate a compromised blood-placental barrier. The absence of PROS1 in fetal vessels may suggest potential complement activation and thrombosis. TYRO3, MERTK, PROS1 and GAS6 may help balance impaired inflammation, apoptosis, thrombosis, complement activation and the blood-placental barrier in PE.