Prostaglandin E2 receptor EP4-selective antagonist inhibits lipopolysaccharide-induced cervical ripening in rabbits

Acta Obstet Gynecol Scand. 2007;86(11):1297-302. doi: 10.1080/00016340701671788.

Abstract

Background: The purpose of this study was to examine whether EP4 as prostaglandin (PG) E2 receptor is involved in lipopolysaccharide (LPS)-induced cervical ripening.

Methods: New Zealand White non-pregnant rabbits were randomly allocated to 4 equal groups and treated with vaginal suppositories containing LPS with various concentrations of EP4-selective antagonist once daily for 3 days, and then sacrificed for analysis. Analysis was performed in order to examine the inhibitory effect of EP4 antagonist on LPS-induced cervical ripening. The expression of EP4 in a cervix treated with LPS was examined immunohistochemically. The percent of cervical extensibility in the segment of cervix as the tensile strength was determined with 5.8 g of constant perpendicular stretching. The ripening area of the cervix with edematous changes in H&E sections was calculated by a microscopic system with a computer-assisted digital analyser. Type-1 collagenase activity was determined in cervical tissue using FITC-labelled type-1 collagen.

Results: Immunohistochemical study shows the positive staining of EP4 at the interstitial cells in the cervix treated with LPS. The extensibility, cervical edematous area and type-1 collagenase activity are significantly reduced in the cervix treated with LPS in the presence of EP4 antagonist compared with that treated with LPS alone.

Conclusions: These data implicates the EP4 as the PGE2 receptor involved in LPS-induced cervical ripening.

MeSH terms

  • Animals
  • Cervical Ripening / drug effects*
  • Cervical Ripening / metabolism
  • Collagenases / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Lipopolysaccharides / pharmacology
  • Models, Animal
  • Naphthalenes / administration & dosage
  • Naphthalenes / pharmacology*
  • Phenylbutyrates / administration & dosage
  • Phenylbutyrates / pharmacology*
  • Pregnancy
  • Rabbits
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E / physiology
  • Receptors, Prostaglandin E, EP4 Subtype
  • Suppositories

Substances

  • 4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid
  • Lipopolysaccharides
  • Naphthalenes
  • Phenylbutyrates
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype
  • Suppositories
  • Collagenases
  • collagenase 1