The effects of retinoic acid on mmp-2 production, proliferation and ultrastructural morphology in rat uterus

Exp Toxicol Pathol. 2017 Oct 2;69(8):643-648. doi: 10.1016/j.etp.2017.06.002. Epub 2017 Jun 22.


Aims: Retinoic acid (RA) has a vital importance in order to ensure continuity and morphology in many tissues. Matrix metalloproteinases (MMPs) have significant roles in proliferation, the formation of cancers, and metastasis. In this study the effects of RA on MMP-2 production in cells of rat uterus were investigated.

Methods: Twenty-four adult Spraque Dawley rats were divided into two groups, the experimental group was treated with 40mg/kg/day 13-cis RA for 5days by gavage. Uterine tissue sections were treated with BrdU and MMP-2 antibodies, evaluated using light microscopy. Tissues were fixed with 2.5% glutaraldehyde and evaluated using transmission electron miroscopy.

Results: MMP-2 immunoreactivity decreased in the stromal cells compared with the control group and no staining of MMP-2 was observed in glandular epithelium in the experimental group. BrDU labeling of cells showed significant decrease in RA-treated group versus control group cells. Based on the electron microscopy evaluation, the surface epithelial cells of the experimental group showed vacuolization, and an accumulation of lipofuscin bodies was also observed in the gland epithelium. Cells involving autophagic vacuoles contained excess lipid granules in the entire uterus layers especially localized at the border of the endometrium and myometrium.

Conclusion: RA had negative effects on cell proliferation and cell morphology and inhibited MMP-2 expression.

Keywords: Immunohistochemistry; Matrix metalloproteinase; Retinoic acid; Ultrastructure; Uterus.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects*
  • Endometrium / drug effects
  • Endometrium / enzymology
  • Endometrium / ultrastructure
  • Female
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Microscopy, Electron, Transmission
  • Myometrium / drug effects
  • Myometrium / enzymology
  • Myometrium / ultrastructure
  • Rats, Sprague-Dawley
  • Tretinoin / pharmacology*
  • Uterus / drug effects*
  • Uterus / enzymology
  • Uterus / ultrastructure*


  • Matrix Metalloproteinase Inhibitors
  • Tretinoin
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat