High glucose condition inhibits trophoblast proliferation, migration and invasion by downregulating placental growth factor expression

J Obstet Gynaecol Res. 2020 Sep;46(9):1690-1701. doi: 10.1111/jog.14341. Epub 2020 Jun 8.

Abstract

Aim: This study aimed to investigate the effect of high glucose (HG) level on the proliferation, migration and invasion of trophoblasts and determine the role of placental growth factor (PLGF) in the process.

Methods: HTR8-S/Vneo was treated with different concentrations of d-glucose (0, 10, 15, 20, 25 and 30 μM) at different times (0, 6, 12 and 24 h). qRT-PCR and Western blot analyses were used to measure PLGF expression. The protein level of PLGF was measured by immunofluorescence. Cell proliferation was assessed with CCK-8 analysis. Wound healing and transwell assays were used to evaluate cell migration and invasion. Intercellular ROS was detected with DCFH-DA.

Results: After d-glucose treatment, the viability decreased in 25 and 30 μM groups. The HG group (25 μM) showed inhibited cell migration and invasion ability. The mRNA and protein levels of PLGF decreased under HG condition. Elevated ROS production was also detected in the HG group. Knocked-down PLGF expression enhanced increased ROS production and decreased cell migration and invasion, which reverted to the original levels after PLGF was overexpressed.

Conclusion: High glucose treatment inhibited HTR8-S/Vneo viability, migration and invasion by downregulating PLGF expression.

Keywords: HTR8-S/Vneo; gestational diabetes mellitus; placental growth factor; pre-eclampsia; reactive oxygen species.

MeSH terms

  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Female
  • Glucose / pharmacology
  • Humans
  • Placenta Growth Factor
  • Pre-Eclampsia*
  • Pregnancy
  • Trophoblasts*

Substances

  • Placenta Growth Factor
  • Glucose