title: Trophoblast mitochondrial function is impaired in preeclampsia and correlates negatively with the expression of soluble fms-like tyrosine kinase 1.
abstract: Preeclampsia is a common medical complication of pregnancy that is associated with significant morbidity and mortality to the mother and the baby. Extensive human epidemiological and experimental studies suggest that excess placental soluble fms-like tyrosine kinase 1, a potent anti-angiogenic factor leads to the maternal hypertension, proteinuria and other systemic complications of preeclampsia. To evaluate the mechanisms of the aberrant placental sFlt1 expression, we studied the role of mitochondrial dysfunction as one possible etiological factor. Here, using human placental samples, we demonstrate that both the activity and expression of a mitochondrial electron transport chain enzyme cytochrome C oxidase (COX) is diminished in the syncytiotrophoblast layer of the chorionic villi from preeclamptic subjects. In addition, there was an inverse correlation between mitochondrial COX enzyme activity and placental sFlt1 expression. Functional in situ enzyme chemistry with electron microscopy also confirmed impaired mitochondrial function in preeclampsia. Ultrastructural and morphometric analysis of mitochondria using electron microscopy demonstrated, that mitochondria are smaller in both the syncytiotrophoblast and cytotrophoblast layers of preeclamptic tissue. The etiology of the mitochondrial dysfunction in preeclampsia as a cause or effect of the placental anti-angiogenic state remains to be elucidated in future studies.
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States. Electronic address: zzsengel@bidmc.harvard.edu.
authors.forename: Zsuzsanna K
authors.initials: ZK
authors.lastname: Zsengellér
authors.affiliation: Emory University, Atlanta, GA, United States.
authors.forename: Augustine
authors.initials: A
authors.lastname: Rajakumar
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Hunter
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
authors.forename: Saira
authors.initials: S
authors.lastname: Salahuddin
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States; Division of Maternal Fetal Medicine/ Obstetrics and Gynecology, University of Chicago Medical Center, Chicago, IL, United States.
authors.forename: Sarosh
authors.initials: S
authors.lastname: Rana
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
authors.forename: Isaac E
authors.initials: IE
authors.lastname: Stillman
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
authors.forename: S
authors.initials: S
authors.lastname: Ananth Karumanchi
mesh_terms: D000328:Adult; D002824:Chorionic Villi / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008854:Microscopy, Electron; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D011225:Pre-Eclampsia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D003576:Electron Transport Complex IV; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenesis; Hypertension; Mitochondria; Oxidative stress; Preeclampsia