Benzoic Acid Enhances Embryo Implantation through LIF-Dependent Expression of Integrin αVβ3 and αVβ5

J Microbiol Biotechnol. 2017 Apr 28;27(4):668-677. doi: 10.4014/jmb.1609.09028.

Abstract

Embryo implantation is the crucial step for a successful pregnancy. Diverse factors, including adhesion molecules, growth factors, and cytokines are important for embryo implantation through improving endometrial receptivity. Benzoic acid (BA), a component of various plants, has been shown to have antifungal and antioxidant effects. However, the effect of BA on embryo implantation remains unknown. Here, we showed the contribution of BA for the enhancement of endometrial receptivity through the leukemia inhibitory factor (LIF)-dependent increase of integrin αV, β3, and β5 expression. Furthermore, in vivo study using a mifepristone-induced implantation failure model showed that BA definitely improves the numbers of implantation embryos. Taken together, we suggest that BA has a novel function for embryo implantation through the up-regulation of LIF-mediated integrins, and may be a candidate for therapeutic medicine to increase the pregnancy rate.

Keywords: Benzoic acid; adhesion; endometrial receptivity; implantation; integrin; leukemia inhibitory factor.

MeSH terms

  • Animals
  • Benzoic Acid / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Embryo Implantation / drug effects*
  • Endometrium / drug effects
  • Estrogen Receptor alpha
  • Female
  • Humans
  • Integrin alphaVbeta3 / metabolism*
  • Leukemia Inhibitory Factor / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Pregnancy Rate
  • RNA, Small Interfering
  • Receptors, Vitronectin / metabolism*
  • Up-Regulation

Substances

  • Cell Adhesion Molecules
  • Cytokines
  • Estrogen Receptor alpha
  • Integrin alphaVbeta3
  • Leukemia Inhibitory Factor
  • RNA, Small Interfering
  • Receptors, Vitronectin
  • integrin alphaVbeta5
  • Benzoic Acid