Activation of Uterine Smad3 Pathway Is Crucial for Embryo Implantation

Curr Med Sci. 2019 Dec;39(6):997-1002. doi: 10.1007/s11596-019-2134-z. Epub 2019 Dec 16.

Abstract

Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors. Transforming growth factor-betas (TGF-βs) and their most specific signal transduction factors, Smads, are expressed in the endometrium during the window of implantation. Recent researches indicated that Smad dependent TGF-β signaling may play an important role in the process of embryo implantation. In this study, we measured the expression of TGF-β1, TGF-β receptor type I (TβRI), Smad3 and p-Smad3 in the endometrium of mice and observed their elevation on day 4, 5 and 6 of pseudopregnancy. Then we administrated a specific Smad3 inhibitor (Sis3) into the uterine cavity of mice on day 3 of pregnancy. The results showed a reduction in insulin-like growth factor-1 (IGFBP-1) expression and the decreased number of implanted embryo after the administration. In addition, Sis3 was found to reduce the IGFBP-1 secretion in decidualized endometrial stromal cells. Taken all together, our findings demonstrated that TGF-β/Smad3 signaling is involved in the process of embryo implantation.

Keywords: Smad3; decidualization; embryo implantation; endometrial receptivity; transforming growth factor-betas (TGF-βs).

MeSH terms

  • Animals
  • Embryo Implantation* / drug effects
  • Female
  • Isoquinolines / administration & dosage
  • Isoquinolines / pharmacology
  • Mice
  • Phosphorylation
  • Pregnancy
  • Pyridines / administration & dosage
  • Pyridines / pharmacology
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology
  • Receptor, Transforming Growth Factor-beta Type I / genetics*
  • Receptor, Transforming Growth Factor-beta Type I / metabolism
  • Signal Transduction
  • Smad3 Protein / antagonists & inhibitors
  • Smad3 Protein / genetics*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation
  • Uterus / metabolism

Substances

  • 6,7-dimethyl-2-(2E)-3-(1-methyl-2-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl-prop-2-enoyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride
  • Isoquinolines
  • Pyridines
  • Pyrroles
  • Smad3 Protein
  • Smad3 protein, mouse
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Receptor, Transforming Growth Factor-beta Type I
  • Tgfbr1 protein, mouse