Physiological role of lysophosphatidic acid.

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Every successful pregnancy requires proper embryo implantation. (a process of particular importance) Poor implantation rate is a major problem during infertility treatments using assisted reproductive technologies (ART). We report a new molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA_3/edg7. Targeted deletion of LPA_3 resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to embryo death or delayed embryonic development and hypertrophic placentas shared by multiple embryos. An enzyme demonstrated to influence implantation, cyclooxygenase-2 (COX-2), was down-regulated in LPA_3-deficient uteri during preimplantation. COX-2 produces prostaglandins that are critical for implantation ^1, and exogenous administration of the prostaglandins PGE_2 and cPGI into LPA_3-deficient females rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA_3 receptor-mediated signaling as a new influence on implantation and further indicate linkage between LPA signalling and prostaglandin biosynthesis.