The role of DRAM1 in mitophagy contributes to preeclampsia regulation in mice

Abstract

Background: Preeclampsia (PE) is a pregnancy complication that is diagnosed by the new onset of hypertension and proteinuria. Although the pathogenesis of PE is still not fully understood, growing evidence indicates that oxidative stress and mitochondrial dysfunction may contribute to the progression of PE. Therefore, we aimed to determine the role of mitophagy in mitochondrial dysfunction and oxidative stress in PE. Moreover, we aimed to evaluate the role of DNA damage-regulated autophagy modulator 1 (DRAM1) in the development of PE. Results: In this study, we first constructed a mouse model of PE induced by Hif-1α and found a high level of oxidative stress, apoptosis and mitochondrial dysfunction in the placentas of PE mice. Additionally, the activity of mitophagy was decreased, and the level of DRAM1 was significantly decreased in the placentas of PE mice. To further explore the role of DRAM1 in mitophagy, DRAM1 was overexpressed in the placental tissues of PE mice. It was found that the overexpression of DRAM1 effectively improved the symptoms of PE mice and that blood lipid and urine protein levels were significantly reduced. Furthermore, DRAM1 overexpression also improved mitochondrial function and reduced oxidative stress in the placentas of PE mice. In addition, it improved mitochondrial fusion and fission and enhanced mitophagy.Conclusions: our results indicate a key role of DRAM1 in mitophagy in contributing to the regulation of PE. To our knowledge, this is the first study to confirm the role of DRAM1 in PE, and the study provides a new understanding of the pathophysiological mechanisms of PE.