Oviducts play roles in reproductive processes, including gametes transport, fertilization and early embryo development. Oviductal transport is controlled by various factors such as endothelins (EDNs) and nitric oxide (NO), smooth muscle contracting and relaxing factor, respectively. EDNs and NO production depend on an ovarian steroid hormone, oestradiol-17β (E2) and E2 quickly exerts their biological functions through G protein-coupled oestrogen receptor 1 (GPER1), which mediates rapid intracellular signalling. Because follicular fluid which contains a high concentration of E2 enters the oviduct, we hypothesized that E2 in the follicular fluid participates via GPER1 in producing EDNs and NO. To test this hypothesis, we investigated 1) the expression and localization of GPER1 in bovine oviductal tissues and 2) rapid effects of E2 via GPER1 on EDN1, EDN2 and inducible NO synthase (iNOS) expression in cultured bovine oviductal isthmic epithelial cells. GPER1 was observed in the oviductal epithelium, stroma and smooth muscle, and its expression was highest in the isthmus. Short-term treatments (≤1 hr) of E2 increased EDN2 mRNA expression in the isthmic epithelial cells, although E2 did not affect EDN1 and iNOS mRNA expressions. Results of GPER1-selective agonist G-1 and GPER1-selective antagonist G-15 treatments revealed acute stimulation by E2, which is mediated via GPER1. The overall findings suggested that E2 in follicular fluid rapidly stimulates EDN2 expression via GPER1 in the isthmic epithelial cells. Follicular fluid may play a role in retention of the ovulated oocyte in the end of ampulla by contracting the isthmus for successful fertilization.

Unidirectional flow of oviductal fluid from the ovarian to uterine side of the ampulla plays a significant role in successful pregnancy, and is produced by ciliary beating. Various systems regulate ciliary beating, such as paracrine, autocrine, and endocrine. We hypothesized that Adrenomedullin (ADM)-a peptide hormone that acts via its receptors, which are complexes of Calcitonin receptor-like receptor (CRLR) and Receptor activity-modifying protein (RAMP) 2 or 3 - promotes oviductal fluid flow in the ampulla of bovine oviducts. First, we examined the expression of ADM, CRLR, RAMP2, and RAMP3 mRNAs in isolated epithelial cells throughout the estrous cycle, and the localization of ADM receptor protein constituents in the ampulla. RAMP2 expression was significantly higher in the follicular phase. Furthermore, RAMP2 protein was detected only in ciliated cells, whereas CRLR and RAMP3 were detected in all epithelial cells. The effects of ADM and an ADM antagonist on fluid-flow speed were examined using microbeads in ampullary tissue. ADM antagonist decreased bead transport speed, and this decrease was reversed by ADM. In addition, ADM recovered the bead transport speed that decreased in the absence of calcium. Overall, our results suggest that ADM contributes to the regulation of oviductal fluid flow in ampulla.