Roles of LPA3 and COX-2 in implantation

Lysophosphatidic acid (LPA) is a lipid-derived G-protein-coupled receptor (GPCR) agonist that is involved in a variety of physiological and pathological processes, including cell survival, proliferation and differentiation, cytoskeletal rearrangement, cell-cell interactions, tumorigenesis and cell invasion. LPA also stimulates oocyte maturation, the preimplantation development of two- or four-cell embryos to the blastocyst stage and embryo transport in the oviduct. Recent studies revealed that targeted deletion of the LPA(3) receptor results in delayed implantation and altered embryo spacing, and significantly reduced litter size in mice. This was attributable to selective downregulation of uterine cyclooxygenase-2 (COX-2), which generates prostaglandins (PGs) E(2) and I(2). Exogenous administration of PGE(2) or the PGI(2) analogue, carba-prostacyclin, to LPA(3)-deficient female mice rescued delayed implantation but did not prevent defects in embryo spacing. These findings indicate that LPA-induced COX-2 induction has a crucial role in implantation and mammalian reproduction.