Accumulation of Dietary and Non-Enzymatic Oxysterols in Preeclamptic Placentas: Insights into Cholesterol Dynamics in Pregnancy Complications

Abstract

Oxysterols--oxidized derivatives of cholesterol--play key roles in regulating lipid metabolism, oxidative stress, and immune signaling. Despite their biological importance, their presence and function in human placental tissue remain poorly understood, particularly in pregnancy complications such as preeclampsia. Preeclampsia is a hypertensive disorder of pregnancy associated with oxidative stress and altered lipid homeostasis. This study profiled both dietary and non-enzymatic oxysterols in third-trimester human placentas from healthy term pregnancies and those complicated with preeclampsia, delivered at term or preterm and term. Findings indicate significantly higher oxysterol levels in preeclamptic placentas, particularly for 7-ketcholesterol (7-Keto) and 5,6{beta}-cholestanetriol, (Triol) regardless of gestational age. 5{beta},6{beta}-epoxycholesterol (OCallaghan, Woods, & OBrien, 2001) was higher in term preeclampsia, while total cholesterol levels were significantly lower in preeclamptic placentas. Correlation analyses revealed distinct associations between oxysterols, cholesterol, and total fat content, indicating unique oxidative signatures in preeclamptic pregnancies. These findings contribute to a growing body of evidence suggesting that altered oxysterol profiles may reflect oxidative stress and placental dysfunction. While causality cannot be inferred, oxysterol profiling may hold potential as a complementary biomarker strategy for identifying pregnancies at risk of adverse outcomes.