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¹ Division of Clinical and Reproductive Sciences and
² Department of Physiology, University of Kentucky, Lexington, Kentucky 40506, USA
³ Pharmacology and Preclinical Development, Actelion Pharmaceuticals Ltd, Allschwil CH-4123, Switzerland
⁴ Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA

(Requests for offprints should be addressed to C Ko; Email: cko2{at}uky.edu)

^* (L Al-Alem and P J Bridges contributed equally to this work)

Proper function of the oviduct is critical to reproductive success with regulated contraction and relaxation facilitating transportation of the germ cells to the site of fertilization. Endothelin-2 (EDN2) is a potent vasoconstrictor produced by granulosa cells of the preovulatory follicle at the time of ovulation; however, whether this gonadotropin surge-induced peptide played a role in facilitating germ cell transportation by inducing oviductal contraction was unknown. The objectives of these experiments were (1) to determine whether the endothelin receptor system was present in the oviduct, (2) to test the hypothesis that EDN2 induces oviductal contraction via a specific endothelin receptor subtype, (3) to determine, as a possible alternate source of the ligand, whether mRNA for EDN2 was expressed in cumulus–oocyte complexes (COCs) within the oviduct, and (4) to determine whether EDN2 could overcome prostaglandin E₂ (PGE₂)-induced oviductal relaxation. Microarray and real-time PCR analysis indicated that mRNA for both the endothelin receptor subtypes (ET_A and ET_B) was present in the oviduct, whereas immunohistochemical examination revealed that ET_A protein was the dominant isoform, present in the luminal epithelial cells of the oviduct. Real-time PCR analysis demonstrated that mRNA for EDN2 was expressed in COCs after ovulation. Isometric tension analysis indicated that EDN2 was a potent oviductal constrictor and that the contractile effect of EDN2 was mediated by the ET_A and not the ET_B receptor subtype. The oviductal contraction induced by EDN2 also reversed oviductal relaxation induced by PGE₂. In summary, ET_A receptor-specific EDN2-induced contraction as a facilitator of oviductal function suggests a novel pathway involved in germ cell transport and hence mammalian fertility.