Lysophosphatidic acid (LPA) has been shown to be a potent modulator of prostaglandin (PG) secretion during the luteal phase of the estrous cycle in the bovine endometrium in vivo. The aims of the present study were to determine the cell types of the bovine endometrium (epithelial or stromal cells) responsible for the secretion of PGs in response to LPA, the cellular, receptor, intracellular, and enzymatic mechanisms of LPA action. Cultured bovine epithelial and stromal cells were exposed to LPA (10−5–10−9 M), tumor necrosis factor α (TNFα; 10 ng/mL) or oxytocin (OT; 10−7 M) for 24 h. LPA treatment resulted in a dose-dependent increase of PGE2 production in stromal cells, but not in epithelial cells. LPA did not influence PGF2α production in stromal or epithelial cells. To examine which type of LPA G-protein–coupled receptor (LP-GPCR; LPA1, LPA2, or LPA3) is responsible for LPA action, stromal cells were preincubated with three selected blockers of LPA receptors: NAEPA, DGPP, and Ki16425 for 0.5 h, and then stimulated with LPA. Only Ki16425 inhibited the stimulatory effect of LPA on PGE2 production and cell proliferation in the stromal cells. LPA-induced intracellular calcium ion mobilization was also inhibited only by Ki16425. Finally, we examined whether LPA-induced PGE2 synthesis in stromal cells is via the influence on mRNA expression for the enzymes responsible for PGE2 synthesis—PGE2synthase (PGES) and PG-endoperoxide synthase 2 (PTGS2). We demonstrated that the stimulatory effect of LPA on PGE2 production in stromal cells is via the stimulation of PTGS2 and PGES mRNA expression in the cells. The overall results indicate that LPA stimulates PGE2 production, cell viability, and intracellular calcium ion mobilization in cultured stromal endometrial cells via Ki16425-sensitive LPA1 receptors. Moreover, LPA exerts a stimulatory effect on PGE2 production in stromal cells via the induction of PTGS2 and PGES mRNA expression.
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