Role of Placental Mitochondria in Development of Pre-eclampsia: Focus on Mitochondrial Dynamics, Redox Signaling and Apoptosis

Abstract

Background: M itochondrial dysfunction has been incriminated in the pathogenesis of preeclampsia (PE). Th is study aimed at evaluating the contribution of mitochondrial dynamics, biogenesis, redox signaling and apoptosis in the pathogenesis of mitochondrial dysfunction in pre-eclamptic placenta. Forty pregnant females were classified equally into two groups: Group І (control group), included normotensive pregnant females and Group ІІ (PE group) included, preeclamptic pregnant females. After delivery, placental tissue samples were collected for estimation of mRNA expression levels of Mitofusin2 (Mfn2) using qu antitative real-time PCR . Dynamin related protein 1 (Drp 1), mitochondrial Cytochrome c release ,and 3-nitrotyrosine (3-NT) were measured by ELISA . M itochondrial co mplex I, and citrate synthase enzyme activity were assessed spectrophotometrically. ATP levels, Caspase-9 activity , inorganic nitrites and nitrate levels ,and superoxide dismutase (SOD) activ ity were measured by colorimetric assay kit. Preeclamptic placentae showed significant decrease in complex I, ATP levels and citrate synthase activity. mRNA expression of Mfn 2 were down regulated with marked elevation of DRP1 protein levels .There were altered redox status as judged by the elevation of NO and protein nitration with reduction in the total SOD activity in pre-eclamptic placentae. There were also activation of the mitochondrial pathway of apoptosis as judged by release of cytochrome c fro m the mitochondrial intermembrane space into the cytosol and significant increase in caspase -9 levels in Pre-eclampt ic placentae compared to controls. Our data strongly nominated significant association between mitochondrial dysfunction, disturbed dynamics, altered redo x status and the susceptibility to apoptosis in pre-eclamptic placenta as key players in the multifactorial pathogenic mechanis ms of PE