105 EFFECT OF LYSOPHOSPHATIDIC ACID ON PROSTAGLANDIN PRODUCTION IN THE BOVINE OVIDUCT

Abstract

The oviduct is an essential organ for successful pregnancy in mammals. The transport of gametes and early embryos is mainly induced by contraction and relaxation of smooth muscle. The contraction and relaxation of bovine oviductal smooth muscle are induced by prostaglandin (PG) F_2α and PGE2, respectively. Lysophosphatidic acid (LPA), a type of phospholipid, is involved in various physiological actions such as promoting inflammation and cellular proliferation in various organs. LPA acts through at least 6 G protein-coupled receptors. Both LPA and LPA receptors are expressed in endometrium and, moreover, LPA affects PG production by the endometrium in cow. Based on the above findings, we hypothesised that LPA is locally involved in PG production by oviductal cells to promote motility of oviductal smooth muscle in cow. Oviductal samples ipsilateral to a corpus luteum or a dominant follicle at peri-ovulation (0–6 and 19–21 days after ovulation) were collected in abattoir. Messenger RNA expression of LPA receptors (LPAR1–6) and LPA-producing enzymes (ATX, PLA1α, PLA1β) was examined in ampullary and isthmic tissues. Expression in cultured epithelial and stromal cells isolated from the bovine oviduct were also examined to determine the cells possessing LPA receptors and LPA-producing enzymes. In addition, the effect of LPA (0.1, 1, 10 μM) on the expression of cyclooxygenase (COX)-1 and COX-2 (PG-synthesising enzymes) and on PGE2 and PGF_2α production by cultured epithelial and stromal cells was investigated. The significant differences (P < 0.05) were determined by Student's t-test for 2 groups, and by one-way ANOVA followed by Tukey's multiple comparison test for more than 3 groups. LPAR1–6, ATX, PLA1α, and PLA1β were expressed in both ampullary and isthmic tissues as well as in both cultured epithelial and stromal cells. The expression of LPAR1–3 was significantly lower in the isthmic tissues than in the ampullary tissues, whereas the expression of LPAR4–6 was significantly higher in the isthmic tissues than in the ampullary tissues. The expression of COX-2 was significantly stimulated by 10 μM LPA in cultured isthmic stromal cells. In addition, LPA significantly stimulated both PGE2 and PGF_2α production by cultured isthmic stromal cells. In the isthmus of the oviduct, LPA produced by epithelial and stromal cells may stimulate the expression of COX-2 in the stromal cells, followed by increased PG production. Because the mRNA expression of LPAR4–6 is higher in the isthmus than in the ampulla, those effects of LPA might be mediated by activation of LPAR4–6. The overall findings suggest that LPA is one of the regulating factors for transport of gametes and early embryos by controlling the motility of smooth muscle in the bovine oviduct.