Mechanism of Placenta Damage in Gestational Diabetes Mellitus by Investigating TXNIP of Patient Samples and Gene Functional Research in Cell Line

Diabetes Ther. 2019 Dec;10(6):2265-2288. doi: 10.1007/s13300-019-00713-z. Epub 2019 Oct 26.

Abstract

Introduction: Gestational diabetes mellitus (GDM) is a gestational complication that affects maternal and child health. The placenta provides the fetus with the necessary nutrition and oxygen and takes away the metabolic waste. Patients with GDM are diagnosed and treated merely on the basis of the blood glucose level; this approach does nothing to help evaluate the status of the placenta, which is worth noting in GDM. The purpose of this research was to clarify the relation between thioredoxin-interacting protein (TXNIP) and reactive oxygen species (ROS) in the placenta of patients with GDM, which has thus far remained unclear.

Methods: The expression of TXNIP in the placentas of 10 patients with GDM and 10 healthy puerperae (control group) was investigated via immunofluorescence. The relation among TXNIP, ROS, and the function of mitochondria was explored in HTR-8/SVneo cells stimulated by high glucose (HG).

Results: The results showed the expression of TXNIP in the placentas of patients with GDM was higher than that in the control group, and the expression of TXNIP in HTR-8/SVneo cells treated with HG was higher than that in the control group, causing the accumulation of ROS and changes of mitochondria, promoting apoptosis and inhibition of migration.

Conclusions: High expression of TXNIP caused by HG mediates the increasing ROS and the mitochondria dysfunction in GDM; this impairs the function of the placenta and is the basis for the prediction of perinatal outcome.

Keywords: GDM; Mitochondria; Placenta; ROS; TXNIP.