Knockdown of CYP1B1 suppresses the behavior of the extravillous trophoblast cell line HTR-8/SVneo under hyperglycemic condition

J Matern Fetal Neonatal Med. 2021 Feb;34(4):500-511. doi: 10.1080/14767058.2019.1610379. Epub 2019 May 2.

Abstract

Introduction: Trophoblast plays a vital role in the embryonic implantation and function of the placenta. Exposure to a hyperglycemic environment results in the abnormal function of trophoblasts during fetoplacental development, which leads to maternal complications and poor fetal outcomes. However, the precise mechanisms of placental pathology during hyperglycemia remain elusive. We investigated the role of CYP1B1 in the functional behavior of the extravillous trophoblast (EVT) cell line HTR-8/SVneo under hyperglycemic condition.Methods: We determined the expression of CYP1B1 via real-time polymerase chain reaction and Western blot. Specific CYP1B1 inhibitors and small interfering RNA were used to knockdown CYP1B1, whereas an agonist and an adenovirus were used to overexpress CYP1B1. The proliferation, migration, and invasion of the EVT cell line (i.e. HTR-8/SVneo) were assessed via colony formation, 5-ethynyl-2-deoxyuridine, wound healing, and transwell assay.Results: CYP1B1 is highly expressed in placentas from women with gestational diabetes mellitus. The blockage of CYP1B1 inhibits EVT activities induced by hyperglycemia in vitro, including proliferation, migration, and invasion, whereas the exogenous expression of CYP1B1 exhibits the opposite effects.Discussion: Our study may offer a new method for regulating EVT motility under hyperglycemic condition via CYP1B1.

Keywords: CYP1B1; GDM; extravillous trophoblasts; high glucose; invasion; proliferation.

MeSH terms

  • Cell Movement
  • Cytochrome P-450 CYP1B1 / genetics
  • Female
  • Humans
  • Hyperglycemia*
  • Placenta
  • Pregnancy
  • Pregnancy Trimester, First
  • Trophoblasts*

Substances

  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1