Abstract. We have previously documented synthesis of lysophosphatidic acid (LPA) in the bovine endometrium and the increased presence of LPA receptor mRNA expression during pregnancy. Therefore, LPA could contribute to early pregnancy establishment in the cow. In the present study, we investigated the effect of intravaginally administered LPA on pregnancy rates and on the plasma levels of progesterone (P4) and prostaglandins (PGs) in heifers. Animals were inseminated and from day 15 to 18 after estrus were treated intravaginally with saline, LPA (1 mg) or LPA receptor blocker (VPC32183; 1 mg). Blood samples were collected on days 0,6,12,15,16,17,18 and 21 after insemination. Pregnancy was confirmed by ultrasonography and per rectum examination on days 30 and 49-50 after insemination. Intravaginal LPA administration increased the plasma P4 and PGE2 concentrations compared with saline and VPC32183-treated heifers. In the saline and LPA-treated groups, 6 out of 8 heifers were pregnant (75%), whereas the pregnancy rate in the VPC32183-treated heifers was only 37%. We also examined the effects of LPA on PG secretion and PG synthase mRNA expression in stromal and epithelial cells of the bovine endometrium on days 16-18 of pregnancy and the estrous cycle. LPA increased PGE2 production and PGE2 synthase (PGES) mRNA expression in stromal cells during the estrous cycle and pregnancy. On Days 16-18 of pregnancy, LPA inhibited PGF2α production and PGFS mRNA expression in epithelial cells. The results suggest that LPA serves as a luteotropic factor during the estrous cycle and pregnancy, stimulating P4 secretion in vivo and PGE2 secretion in vitro through activation of PGES mRNA expression in stromal cells. Moreover, during the early pregnancy, LPA decreases PGF2α synthesis and mRNA expression for PGFS in epithelial cells of the bovine endometrium. Key words: Cow, Lysophosphatidic acid, Pregnancy, Progesterone, Prostaglandins (J. Reprod. Dev. 56: [411][412][413][414][415][416][417][418][419][420] 2010) he role of lysophosphatidic acid (LPA) in the reproductive system has been studied extensively in mice [1], pigs [2,3], ewes [4] and cows [5][6][7]. We found that in the bovine endometrium, in contrast to the mouse, pig and sheep [1][2][3][4], there is mRNA expression only for the LPA receptor type 1 (LPAR1) [5]. We also demonstrated that LPA is locally produced and released from the bovine endometrium [5]. The LPA concentration and expression of mRNA for LPAR1 in the bovine endometrium are significantly higher during early pregnancy than during the estrous cycle. Moreover, LPA administered into the aorta abdominalis stimulated progesterone (P4) and prostaglandin (PG) E2 secretion during the luteal phase of the estrous cycle in vivo. This LPA-mediated stimulation of PGE2 synthesis might serve as an additional luteotropic factor during the luteal phase of the estrous cycle and on days 8-10 of early pregnancy. However, during early pregnancy, on days 8-10 after conception in the cow, LPA may play an even more important role b...