Abstract
OBJECTIVE: To determine factors differentiating LPA3 from other lysophospholipid (LP) receptors for its role in embryo implantation. DESIGN: Experimental mouse models. SETTING: Institute/university research laboratories. ANIMAL(S): Wild-type, Lpar3(-/-), Lpar1(-/-)Lpar2(-/-), and S1pr2(-/-)S1pr3(-/-) mice. INTERVENTION(S): Ovariectomy. MAIN OUTCOME MEASURE(S): Blue dye injection for determining implantation sites on gestation day 4.5. Real-time polymerase chain reaction for measuring gene expression in whole uterus and separated uterine layers. In situ hybridization for detecting progesterone (P)-induced Lpar3 expression in the uterine luminal epithelium (LE). RESULT(S): Normal implantation was observed in Lpar1(-/-)Lpar2(-/-) and S1pr2(-/-)S1pr3(-/-) females. Temporal expression showed peak expression of Lpar3 in the preimplantation uterus and constitutive expression of the other nine LP receptors in the periimplantation uterus. Spatial localization revealed main expression of Lpar3 in the LE and broad expression of the remaining LP receptors in all three main uterine layers: LE, stromal, and myometrial layers. Hormonal regulation in ovariectomized uterus indicated up-regulation of Lpar3 but down-regulation or no effect of the remaining nine LP receptors by P, and down-regulation of most LP receptors, including Lpar3, by 17β-estradiol. CONCLUSION(S): LE localization and up-regulation by P differentiate LPA3 from the other nine LP receptors and may underlie its essential role in embryo implantation.