Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2021; 12(11): 1894-1907
Published online Nov 15, 2021. doi: 10.4239/wjd.v12.i11.1894
p66Shc-mediated oxidative stress is involved in gestational diabetes mellitus
Ting-Ting Huang, Wen-Juan Sun, Hai-Ying Liu, Hong-Li Ma, Bao-Xia Cui
Ting-Ting Huang, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong Province, China
Ting-Ting Huang, Hong-Li Ma, Department of Obstetrics, Taian City Central Hospital, Taian 271000, Shandong Province, China
Wen-Juan Sun, Department of Obstetrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong Province, China
Hai-Ying Liu, Department of Obstetrics and Gynecology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266000, Shandong Province, China
Bao-Xia Cui, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, Shandong Province, China
Author contributions: Huang TT, Sun WJ, Liu HY, and Cui BX designed and coordinated the study; Huang TT, Sun WJ, and Ma HL performed the experiments, acquired, and analyzed the data; Huang TT, Sun WJ, and Liu HY interpreted the data; Huang TT and Sun WJ wrote the manuscript; All authors approved the final version of the article.
Supported by The Scientific Research Fund of Qilu Hospital (Qingdao), No. QDKY2015ZD04.
Institutional review board statement: The study was reviewed and approved by the Taian City Central Hospital Institutional Review Board (Approval NO. 2016-05-15).
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Bao-Xia Cui, PhD, Chief Physician, Professor, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wenhua Xi Road, Jinan 250013, Shandong Province, China.
Received: July 22, 2021
Peer-review started: July 22, 2021
First decision: August 16, 2021
Revised: August 29, 2021
Accepted: September 19, 2021
Article in press: September 19, 2021
Published online: November 15, 2021
Research background

Oxidative stress and mitochondrial dysfunction in the placenta are closely related to the onset of gestational diabetes mellitus (GDM). p66Shc plays a role in regulating mitochondrial oxidative stress, and dynamin-related protein 1 (Drp1) is a necessary dynamic protein for mitosis of primarily localized mitochondria.

Research motivation

The motivation was to add to what is known of the role of placental mitochondria in the etiology of GDM.

Research objectives

The study aimed to investigate the potential mechanism of p66Shc in GDM.

Research methods

We detected the expression of Drp1 and p66Shc in patients with GDM and investigated the possible pathogenesis of GDM through in vitro culture of the JEG3 human trophoblast line.

Research results

P66Shc, Drp1, and reactive oxygen species (ROS) were highly expressed in the placentas and peripheral blood during GDM and in JEG3 cells under high glucose conditions. A significant increase in the expression of Drp1 and the level of ROS was detected in JEG3 cells overexpressing activated p66Shc. In contrast, p66Shc knockdown reduced the expression of Drp1 and the level of ROS.

Research conclusions

The increased expression of p66Shc induced by high glucose-activated Drp1 and promoted ROS overproduction, which may contribute to the occurrence and development of GDM.

Research perspectives

This study may provide a new understanding of molecular mechanism and experimental basis for the role of mitochondrial damage in the pathogenesis of gestational diabetes mellitus and provide a new approach for the treatment of the condition and its complications.