Annexin A1/Formyl Peptide Receptor Pathway Controls Uterine Receptivity to the Blastocyst

C.B. Hebeda, S. Sandri, C.M. Benis, M. de Paula-Silva, R.A. Loiola, C. Reutelingsperger, M. Perretti, S.H.P. Farsky*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

Embryo implantation into the uterine wall is a highly modulated, complex process. We previously demonstrated that Annexin A1 (AnxA1), which is a protein secreted by epithelial and inflammatory cells in the uterine microenvironment, controls embryo implantation in vivo. Here, we decipher the effects of recombinant AnxA1 in this phenomenon by using human trophoblast cell (BeWo) spheroids and uterine epithelial cells (Ishikawa; IK). AnxA1-treated IK cells demonstrated greater levels of spheroid adherence and upregulation of the tight junction molecules claudin-1 and zona occludens-1, as well as the glycoprotein mucin-1 (Muc-1). The latter effect of AnxA1 was not mediated through IL-6 secreted from IK cells, a known inducer of Muc-1 expression. Rather, these effects of AnxA1 involved activation of the formyl peptide receptors FPR1 and FPR2, as pharmacological blockade of FPR1 or FPR1/FPR2 abrogated such responses. The downstream actions of AnxA1 were mediated through the ERK1/2 phosphorylation pathway and F-actin polymerization in IK cells, as blockade of ERK1/2 phosphorylation reversed AnxA1-induced Muc-1 and claudin-1 expression. Moreover, FPR2 activation by AnxA1 induced vascular endothelial growth factor (VEGF) secretion by IK cells, and the supernatant of AnxA1-treated IK cells evoked angiogenesis in vitro. In conclusion, these data highlight the role of the AnxA1/FPR1/FPR2 pathway in uterine epithelial control of blastocyst implantation.
Original languageEnglish
Article number1188
Number of pages17
JournalCells
Volume9
Issue number5
DOIs
Publication statusPublished - 1 May 2020

Keywords

  • 2 pathway
  • a1
  • actin
  • angiogenesis
  • barrier
  • bewo spheroids
  • breast-cancer
  • claudin-1
  • erk1
  • f-actin polymerization
  • human amnion
  • human fetal membranes
  • implantation
  • in-vitro
  • ishikawa cells
  • muc1 expression
  • mucin-1
  • proteins
  • zona occludens
  • Ishikawa cells
  • HUMAN FETAL MEMBRANES
  • BeWo spheroids
  • BREAST-CANCER
  • A1
  • IN-VITRO
  • ERK1
  • IMPLANTATION
  • ACTIN
  • F-actin polymerization
  • BARRIER
  • MUC1 EXPRESSION
  • HUMAN AMNION
  • PROTEINS

Cite this