Every successful pregnancy requires proper embryo implantation. Low implantation rate is a major problem during infertility treatments using assisted reproductive technologies. Here we report a newly discovered molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA₃ (refs ). Targeted deletion of LPA₃ in mice resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to delayed embryonic development, hypertrophic placentas shared by multiple embryos and embryonic death. An enzyme demonstrated to influence implantation, cyclooxygenase 2 (COX2) (ref. ), was downregulated in LPA₃-deficient uteri during pre-implantation. Downregulation of COX2 led to reduced levels of prostaglandins E₂ and I₂ (PGE₂ and PGI₂), which are critical for implantation. Exogenous administration of PGE₂ or carbaprostacyclin (a stable analogue of PGI₂) into LPA₃-deficient female mice rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA₃ receptor-mediated signalling as having an influence on implantation, and further indicate linkage between LPA signalling and prostaglandin biosynthesis.