The role of mitochondria in early-onset preeclampsia
Abstract
[EMBARGOED UNTIL 12/1/2024] Placental mitochondrial dysfunction may play a role in the etiology of early-onset preeclampsia (EOPE). Mitochondrial function is impaired at term in placentas delivered from EOPE pregnancies, but it is not known whether this dysfunction is present early in gestation. Oxidative phosphorylation (OXPHOS), which occurs in the mitochondria, is essential for trophoblast function. Understanding mitochondrial dynamics in normal and EOPE cells of early pregnancy is important for assessing the cause of EOPE. Modeling preeclampsia remains difficult due to the nature of the disease and the unique characteristics of the human placenta. Members of the hominoidea superfamily have a villous hemochorial placenta that is different in structure from other therian mammals, including the mouse hemochorial placenta, making this common animal model less ideal for studying this disease. Human placental tissues delivered from pregnancies complicated by preeclampsia are excellent for assessing the damage the disease causes but cannot answer how or when the disease begins. Symptoms of preeclampsia manifest halfway through pregnancy or later, making it currently impossible to identify preeclampsia in human tissues obtained from an early stage of pregnancy. Many animal and cell culture models recapitulate various aspects of preeclampsia, though none can on its own completely capture the complexity of human preeclampsia. It is particularly difficult to uncover the cause of the disease by using models in which the disease is induced in the lab. However, the many ways by which preeclampsia-like features can be induced in a variety of laboratory animals are consistent with the idea that preeclampsia is a multifactorial disease. The recent development of stem cell- based models, organoids, and various coculture systems have brought in vitro systems with human cells ever closer to recapitulating in vivo events. This review will discuss placental development and maturation, mitochondrial function, and approaches to modeling preeclampsia.
Degree
Ph. D.