A perinatal approach for unraveling mitochondrial function in preeclampsia and fetal growth restriction: a role for mitochondrial-targeted therapies

Abstract

Preeclampsia (PE) is a complex hypertensive disorder resulting from placental insufficiency during pregnancy. PE contributes to maternal and fetal morbidity and mortality and often co-occurs with fetal growth restriction (FGR); these two are both considered placental insufficiency syndromes. Alterations in mitochondrial function levels due to placental insufficiency play an important role in the pathophysiology of PE and FGR. Changes in these processes can lead to maternal and fetal organ damage with subsequent risk to develop cardiovascular disease. This review therefore investigates the effects of placental insufficiency syndromes, including PE and FGR, on mitochondrial function and its underlying mechanisms, using a perinatal approach including maternal heart and kidney, placenta, and fetal heart and kidney. This review also explores the potential of mitochondrial-targeted therapies in mitigating these effects. We provide an overview of the literature at hand and demonstrate the critical role of mitochondrial function in different organ systems. Subsequently, we also discuss the need for mitochondrial-targeted therapies, in particular, focused on oxidative stress, metabolic pathways, mitochondrial quality control, and mitochondrial calcium handling. This knowledge provides guidance for future studies and potential therapies to improve PE and FGR and their consequences for maternal and fetal outcomes during pregnancy and cardiovascular health later in life.