Serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) inhibits the rat embryo implantation in vivo and interferes with cell adhesion in vitro

Contraception. 2011 Dec;84(6):642-8. doi: 10.1016/j.contraception.2011.03.017. Epub 2011 May 8.

Abstract

Background: This study was conducted to observe the in vivo effect of 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) on embryo implantation in rats and its in vitro effect on cell adhesion.

Study design: The anti-implantation efficacy of AEBSF in rats was determined by counting the number of visible implanted embryos on day 8 of pregnancy following intrauterine (5 mg and 10 mg AEBSF per horn) or tail vein (10 mg AEBSF per rat) administration on day 3 of pregnancy. The effects of AEBSF on cell adhesion were detected, respectively, by using the mouse blastocysts-endometrial cells or the human umbilical vein endothelial cells (HUVECs)-HeLa cells co-culture model. The alteration in protein secretion pattern of HUVECs and HeLa cells was detected by the proteome analysis.

Results: 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride showed an in vivo inhibitory effect on embryo implantation in rat. In vitro, AEBSF could disturb the growth of blastocysts on endometrial cells and inhibit the adhesion of HeLa cells on HUVECs. The treatment of AEBSF could alter the protein secretion pattern of co-cultured HUVEC-HeLa cells.

Conclusion: 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride might be a potential leading compound for novel contraceptives, and its inhibitory effect on implantation might result from the interference in extracellular matrix remodeling process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Animals
  • Blastocyst / drug effects
  • Cell Adhesion / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Contraceptives, Postcoital, Synthetic / administration & dosage
  • Contraceptives, Postcoital, Synthetic / pharmacology
  • Dose-Response Relationship, Drug
  • Embryo Implantation / drug effects*
  • Endometrium / cytology
  • Endometrium / drug effects
  • Female
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Injections, Intravenous
  • Mice
  • Mice, Inbred ICR
  • Pregnancy
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / pharmacology*
  • Sulfones / administration & dosage
  • Sulfones / pharmacology*

Substances

  • Contraceptives, Postcoital, Synthetic
  • Serine Proteinase Inhibitors
  • Sulfones
  • 4-(2-aminoethyl)benzenesulfonylfluoride