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

Document Type : Original Article

Authors

1 Departments of Medical Biochemistry, Faculty of Medicine, Tanta University

2 Department of Medical Biochemistry, Faculty of Medicine, Tanta University

3 Department of Obstetrics and Gynecology, Faculty of Medicine, Tanta University

Abstract

Background: Mitochondrial dysfunction has been incriminated in the pathogenesis of pre-eclampsia (PE). This 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, pre-eclamptic pregnant females. After delivery, placental tissue samples were collected for estimation of mRNA expression levels of Mitofusin2 (Mfn2) using quantitative real-time PCR . Dynamin related protein 1 (Drp1), mitochondrial Cytochrome c release ,and 3-nitrotyrosine (3-NT) were measured by ELISA . Mitochondrial complex I, and citrate synthase enzyme activity  were assessed  spectrophotometrically. ATP levels, Caspase-9 activity , inorganic nitrites and nitrate  levels ,and superoxide dismutase (SOD) activity were measured  by colorimetric assay kit. Pre-eclamptic placentae showed significant decrease in complex I, ATP levels and citrate synthase activity. mRNA expression  of Mfn2 were downregulated 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 from the mitochondrial intermembrane space into the cytosol and significant increase in caspase-9 levels in Pre-eclamptic placentae compared to controls. Our data strongly nominated significant association between mitochondrial dysfunction, disturbed dynamics, altered redox status and the susceptibility to apoptosis in pre-eclamptic placenta as key players in the multifactorial pathogenic mechanisms of PE

Keywords

Bulletin of Egyptian Society for Physiological Sciences
Volume 38, Issue 1
January 2022
Pages 38-52

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