Alterations in antioxidant system, mitochondrial biogenesis and autophagy in preeclamptic myometrium

Polina A Vishnyakova,Maria A Volodina,Nadezhda V Tarasova,Maria V Marey,Natalya E Kan,Zulfiya S Khodzhaeva,Mikhail Yu Vysokikh,Gennady T Sukhikh

doi:10.1016/j.bbacli.2017.06.002

Abstract

Preeclampsia is a pregnancy complication which causes significant maternal and fetal morbidity and mortality worldwide. Although intensive research has been performed in the last 40years, the pathology of preeclampsia is still poorly understood. The present work is a comparative study of the myometrium of women with normal pregnancy, and those with late- and early-onset preeclampsia (n=10 for each group). We observed significant changes in the levels of antioxidant enzymes, markers of mitochondrial biogenesis and autophagy proteins in preeclamptic myometrium. Levels of superoxide dismutase 1 and catalase were lower in both preeclamptic groups than the control group. In late-onset preeclampsia, expression levels of essential mitochondria-related proteins VDAC1, TFAM, hexokinase 1, PGC-1α and PGC-1β, and autophagy marker LC3A, were significantly elevated. In the myometrium of the early-onset preeclampsia group OPA1 and Bcl-2 were up-regulated compared to those of the control (p<0.05). These findings suggest that crucial molecular changes in the maternal myometrium occur with the development of preeclampsia.

Highlights

Preeclampsia (PE) is a multisystem disorder which affects approximately 6% of pregnant women worldwide, and still remains a leading cause of maternal and perinatal morbidity and mortality [1,2]
There are two clinically-distinct PE phenotypes that vary in the time of onset: early-onset PE, which occurs before 34 weeks, and late-onset PE, which takes place after 34 weeks of gestation [3]
We investigated whether markers of mitochondrial quantity and biogenesis in the myometrium change as a result of PE development

Summary

Introduction

Preeclampsia (PE) is a multisystem disorder which affects approximately 6% of pregnant women worldwide, and still remains a leading cause of maternal and perinatal morbidity and mortality [1,2]. Very few studies have focused on the antioxidant system, mitochondrial apparatus and autophagy in myometrium, despite them being highly interconnected [15]. Free radicals, derived from preeclamptic placenta, induce the circulation of reactive oxygen species (ROS) and oxidation products of biomolecules in the blood. This may affect the functionality of myometrium and endothelial cells by influencing a wide range of cellular processes [10]. Since mitochondria and NADPH oxidase are considered major sources of ROS in PE placentas [16,17], it is important to evaluate the expression of antioxidant enzymes, state of ROS-sensitive mitochondrial network [18], and level of autophagy in the neighbouring myometrium

Methods

Results

Conclusion