Published online Nov 15, 2021. doi: 10.4239/wjd.v12.i11.1894
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
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.
The motivation was to add to what is known of the role of placental mitochondria in the etiology of GDM.
The study aimed to investigate the potential mechanism of p66Shc in GDM.
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.
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.
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.
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.