Fibroblast Growth Factor 7 Regulates Proliferation and Decidualization of Human Endometrial Stromal Cells via ERK and JNK Pathway in an Autocrine Manner

Reprod Sci. 2017 Dec;24(12):1607-1619. doi: 10.1177/1933719117697122. Epub 2017 Mar 7.

Abstract

Decidualization is an essential activity of the endometrium in pregnancy, but the molecular mechanisms involving the initiation and maintenance have not yet been clarified. In the present study, we examined the expression of fibroblast growth factor 7 (FGF7) in endometria, normal decidua, and abortion decidua from miscarriage by immunohistochemistry. We analyzed the expression of FGF7 and FGFR2 and the levels of phosphorylated extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK) in endometrial stromal cells (ESCs), and decidual stromal cells (DSCs) from early pregnancy or miscarriage by In-Cell Western assay. The effect of FGF7 on the proliferation of decidualized ESCs was determined by bromodeoxyuridine proliferation assay. Our results show that the expression of FGF7 protein in the normal decidua is obviously higher than that of the endometrium and the abortion decidua, and the expression of FGF7 in the abortion decidua was still higher than that in the endometrium. The FGF7 expression in ESCs is significantly increased after stimulation with a combination of progesterone and 17β-estradiol or 8-bromoadenosine 3',5'-cyclic monophosphate for 12 days. The expression of FGF7 and FGFR2 and the levels of phosphorylated ERK and JNK in DSCs from normal decidua are markedly higher compared with that in ESCs from the endometrium, and the DSCs from abortion decidua had lower expression than DSCs from normal decidua but still higher than ESCs from the endometrium. Our results suggest that FGF7 may stimulate ESCs proliferation and insulin-like growth factor-binding protein 1 and prolactin expressions through ERK and JNK signal pathways in an autocrine manner.

Keywords: DSCs; ESCs; FGF7; decidualization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autocrine Communication*
  • Cell Proliferation*
  • Decidua / metabolism*
  • Female
  • Fibroblast Growth Factor 7 / metabolism*
  • Humans
  • MAP Kinase Signaling System*
  • Phosphorylation
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Stromal Cells / metabolism*
  • Up-Regulation

Substances

  • FGF7 protein, human
  • Fibroblast Growth Factor 7
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2