Spatial and Temporal Analyses of FGF9 Expression During Early Pregnancy

Cell Physiol Biochem. 2017;42(6):2318-2329. doi: 10.1159/000480004. Epub 2017 Aug 17.

Abstract

Background: Fibroblast growth factors (FGFs), in complex with their receptors (FGFRs), regulate a broad spectrum of biological functions including cellular proliferation, survival, migration, and differentiation. In human endometrial stromal cells, FGF9 is regulated with estrogen (E).

Methods/results: First, we report that in uterus tissue of ovariectomized wild type mice, FGF9 is present in three isoforms and is regulated with E. Second, we found that during peri-implantation, Fgf9 expression reached its peak at day 4.5 of pregnancy. Immunofluorescence analyses demonstrated overlapping FGF9 and COX2 expression surrounding the blastocyst attachment site. Next, we identified FGF9- and CD31-positive cells as a part of the microvessels; however, expression was localized to a distinct population of cells. Finally, our data showed synchronized, spatial expression of FGF9 on the luminal epithelium with FGFR2 present on the trophectoderm.

Conclusion: Our data suggest that FGF9 is a crucial factor required to establish the appropriate microenvironment for successful implantation and the maintenance of pregnancy.

Keywords: Angiogenesis; Fibroblast growth factor 9 (FGF9); Fibroblast growth factor receptor (FGFR); Implantation.

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Embryo Implantation
  • Female
  • Fibroblast Growth Factor 9 / genetics
  • Fibroblast Growth Factor 9 / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Fluorescence
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Pregnancy
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Uterus / metabolism
  • Uterus / pathology

Substances

  • Fibroblast Growth Factor 9
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Protein Isoforms
  • RNA, Messenger
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Receptor, Fibroblast Growth Factor, Type 2