Progesterone-induced miR-152 interferes with embryonic implantation by downregulating GLUT3 in endometrial epithelium

Am J Physiol Endocrinol Metab. 2019 Apr 1;316(4):E557-E567. doi: 10.1152/ajpendo.00245.2018. Epub 2019 Jan 22.

Abstract

To investigate the role of progesterone-induced micro-RNA (miR)-152 in early embryonic development and implantation by regulating GLUT3 in endometrial epithelium, qRT-PCR was used to detect the expression of miR-152, GLUT1, and GLUT3 in the endometrial epithelial cells of female mice. GLUT1 and GLUT3 proteins were detected by immunohistochemical staining in the mouse endometrial epithelium. Bioinformatics prediction associated with a luciferase assay was performed to determine whether GLUT1 and GLUT3 are target genes of miR-152. Specific miR-152 mimics or inhibitors were transfected into the endometrial epithelial cells to, respectively, overexpress or downregulate miR-152. Next, the glucose concentration of uterine fluid was measured by conducting high-performance liquid chromatography in vivo, and the glucose uptake of the endometrial epithelial cells was observed using a fluorometric assay in vitro. Early embryonic development and implantation were also observed after the miR-152 mimics or inhibitors had been transfected. Embryo transfer was observed after the miR-152 mimic transfection. miR-152 was found to directly target and thereby downregulate GLUT3 expression. The expressions of both miR-152 and GLUT3 in the mouse endometrial epithelium had spatiotemporal characteristics on days 1-4 of pregnancy. miR-152 affected the glucose concentration of uterine fluid and the glucose uptake of endometrial epithelial cells. The transfection of specific miR-152 mimics led to impaired embryonic development and implantation. To conclude, in endometrial epithelial cells, progesterone-induced miR-152 downregulates GLUT3 at the posttranscriptional level to maintain a proper glucose concentration in the uterine fluid, which is necessary for early embryonic development and implantation.

Keywords: embryonic development and implantation; endometrial epithelial cells; glucose transporter 3; miR-152; uterine fluid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Down-Regulation
  • Embryo Implantation*
  • Embryonic Development
  • Endometrium / metabolism*
  • Epithelial Cells / metabolism
  • Extracellular Fluid / metabolism*
  • Female
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / genetics*
  • Glucose Transporter Type 1 / metabolism
  • Glucose Transporter Type 3 / genetics*
  • Glucose Transporter Type 3 / metabolism
  • Mice
  • MicroRNAs / metabolism*
  • Progesterone / metabolism*
  • Uterus

Substances

  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • MIRN152 microRNA, mouse
  • MicroRNAs
  • Slc2a1 protein, mouse
  • Slc2a3 protein, mouse
  • Progesterone
  • Glucose