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Localization and steroid regulation of prostaglandin E₂ receptor protein expression in ovine cervix

Maternité Port-Royal, Hopital Cochin, AP-HP, Université René Descartes Paris V, Boulevard de Port-Royal, 75014 Paris, France, ¹ New York University School of Medicine, New York 10016, USA and ² Center for Pregnancy and Newborn Research, University of Texas Health Sciences Center, Medical School, Department of Obstetrics and Gynecology, San Antonio, Texas 78229, USA

Correspondence should be addressed to T Schmitz; Email: thomas.schmitz{at}cch.aphp.fr

Although prostaglandin E₂ (PGE₂) has been identified as a central mediator of the cervical ripening process, the mechanisms responsible for PGE₂ ripening are still poorly understood, partly because of the lack of information concerning the precise cellular localization and regulation of PGE₂ (EP) receptors in the cervix. To provide new insights into the mechanisms of cervical ripening, we used indirect immunofluorescence to localize cervical EP receptor protein expression in ovariectomized ewes and examined the effect of administration of progesterone or estradiol. EP receptors were widely distributed in cervical blood vessels, epithelium of the cervical canal, circular and longitudinal muscles, and stroma. Estradiol replacement decreased EP₁ and EP₃ receptor protein in blood vessel media (by 23 and 31% respectively, P < 0.05) and decreased EP₁ receptor protein expression in the longitudinal muscle layer (by 27%, P < 0.05). Stromal EP₁ and EP₃ receptor protein expression was also reduced by estradiol (by 29 and 20% respectively, P < 0.05). Progesterone replacement had no significant effect on EP receptor protein expression. The arterial changes would favor PGE₂-induced vasodilatation, subsequent edema and leukocyte infiltration during the cervical ripening process whereas the muscular alterations would facilitate smooth muscle relaxation and cervical dilatation. Furthermore, estradiol provoked perinuclear localization of EP₃ receptor protein in the longitudinal muscle layer. This latter result suggests that cellular EP receptor localization is regulated by estradiol and that PGE₂ may also control smooth muscle contraction and regulate ovine cervical dilatation in an intracrine manner via EP₃ receptors.