Lysophosphatidic acid (LPA) modulates prostaglandin (PG) synthesis via LPA receptor 3 (LPAR3) in the murine endometrium. The lack of functional LPAR3 in mice may lead to embryo mortality. In the present study, we examined the role of LPA in the bovine uterus. We confirmed that LPA is locally produced and released from the bovine endometrium. Moreover, there are enzymes involved in LPA synthesis (phospholipase (PL) D 2 and PLA2G1B) in the bovine endometrium during estrous cycle and early pregnancy. Expression of the receptor for LPA (LPAR1) was positively correlated with the expression of PGE 2 synthase (PGES) and negatively correlated with the expression of PGF 2a synthase (aldose reductase with 20 a-hydroxysteroid dehydrogenase activity -PGFS) during early pregnancy. In vivo LPA induced P4 and PGE 2 secretion was inhibited by LPAR1 antagonist (Ki16425). The overall results indicate that LPA is locally produced and released from the bovine endometrium. Moreover, LPAR1 gene expression in the endometrium during the estrous cycle and early pregnancy indicates that LPA may play autocrine and/or paracrine roles in the bovine uterus. LPAR1 gene expression is positively correlated with the expression of the enzyme responsible for luteotropic PGE 2 production (PGES) in endometrium. In cow, LPA stimulates P4 and PGE 2 secretion. Thus, LPA in the bovine reproductive tract may indirectly (via endometrium) or directly support corpus luteum action via the increase of P4 synthesis and the increase of PGE 2 /PGF 2a ratio. It suggests that LPA may serve as an important factor in the maintenance of early pregnancy in cow. Reproduction (2009) 137 95-105

Abstract. Lysophosphatidic acid (LPA) is becoming a new player in regulation of the reproductive processes of domestic animals. In the present study, we examined whether LPA modulates prostaglandin (PG) synthesis in the bovine endometrium at the time of the early maternal pregnancy recognition compared with the respective days of the estrous cycle and the enzymatic mechanism of this action. Bovine epithelial and stromal endometrial cells isolated from the uteri on days 8-10 of the estrous cycle and pregnancy were cultured with LPA for 24 h. LPA increased PGE2 production in stromal cells during the estrous cycle and early pregnancy. On days 8-10 of pregnancy, LPA inhibited PGF2α production in epithelial cells. LPA stimulated PGES mRNA expression in stromal cells during both examined phases and inhibited PGFS mRNA expression in epithelial cells on days 8-10 of pregnancy. The overall results indicate that LPA may serve as a luteotropic factor during the luteal phase of the estrous cycle and early pregnancy stimulating PGE2 synthesis and mRNA expression for PGES in stromal cells. Moreover, during early pregnancy, LPA might protect bovine CL and early embryo development by decreasing PGF2α synthesis and mRNA expression for PGFS in the epithelial cells of the bovine endometrium. Key words: Cow, Lysophosphatidic acid, Prostaglandins, Uterus (J. Reprod. Dev. 55: [393][394][395][396][397][398][399] 2009) ysophosphatidic acid (LPA), a simple phospholipid, has a vast variety of physiological and pathological actions, such as cell proliferation and differentiation [1,2], cytoskeletal rearrangement [3], cell-to-cell interactions [4] and tumorigenesis [5,6]. In the literature, at least two pathways of LPA synthesis have been postulated [7,8]. In serum and plasma, LPA is mainly converted from lysophospholipids [8]. By contrast, in platelets and some cancer cells, LPA is converted from phosphatidic acid. In each pathway, at least two phospholipase activities are required; phospholipase A1 (PLA1)/PLA2 plus lysophospholipase D (lysoPLD) activities are involved in the first pathway, and phospholipase D (PLD) plus PLA1/PLA2 activities are involved in the second pathway [7]. In the reproductive system, the LPA role has been studied extensively so far. We have recently found that in the bovine endometrium, unlike in mice, pigs and sheep [9][10][11][12], there is only mRNA expression for the receptor for LPA type 1 (LPA1) [13]. We also found that LPA is locally produced and released from the bovine endometrium [13]. The lysophosphatidic acid concentration and expression of mRNA for LPA1 in the bovine endometrium are significantly higher during early pregnancy than during the estrous cycle. Moreover, LPA stimulates progesterone (P4) and prostaglandin (PG) E2 secretion in vivo, and its receptor gene expression (LPA1) is positively correlated with expression of the enzyme responsible for luteotropic PGE2 production (PGES) in the bovine endometrium during the estrous cycle and early pregnancy. These data indicate that LPA may play auto...

Abstract. The present study compared the changes in isoflavones (daidzein and genistein) and their metabolite (equol and para-ethyl-phenol) concentrations in the blood plasma of cyclic and pregnant heifers after feeding with soy bean. Twelve healthy heifers were divided into three groups: cyclic heifers (days 8-12 of the estrous cycle; control group; n= 4), an early pregnancy group (2 months pregnant; n=4) and a late pregnancy group (8 months pregnant; n=4). All heifers were fed a single dose of 2.5 kg of soy bean and then blood samples were taken from the jugular vein for 8 h at predetermined intervals. The concentrations of soy bean-derived isoflavones and their active metabolites were measured in the blood plasma on an HPLC system. In the blood plasma of the early-and late-pregnant heifers, we found lower concentrations and time-dependent decreases in daidzein and genistein in comparison to cyclic heifers (P<0.05). Moreover, we noticed significant increases of equol and para-ethyl-phenol in the blood plasma of the earlypregnant heifers (P<0.05). In contrast, in the blood plasma of the late-pregnant heifers, we did not find an increase in the isoflavone metabolite concentrations compared with the early-pregnant heifers (P>0.05). In conclusion, physiological status (cyclicity or pregnancy) of the females influenced the concentrations of isoflavone metabolites in the blood plasma of the heifers. The stage of pregnancy affects isoflavone absorption, biotransformation and metabolism differently and results in higher concentrations of active metabolites of isoflavones during early pregnancy in comparison to their lower concentrations during late pregnancy. Therefore, we surmise that cows are more sensitive to active isoflavone metabolite actions during early pregnancy than cyclic heifers and heifers in late pregnancy. Key words: Cow, Estrous cycle, Isoflavone, Phytoestrogen, Pregnancy (J. Reprod. Dev. 54: [358][359][360][361][362][363] 2008) ost of the fodder commonly used for feeding ruminants has been reported to contain phytoestrogens. In particular, alfalfa, red clover and soy bean contain 5 to even 25% phytoestrogens, such as coumestrol, genistein, daidzein, formonentin and biochanin A [1][2][3]. Red clover silage containing isoflavones [1], alfalfa containing coumestrans [4] as well as soy bean containing up to 25% of daidzein and genistein have been reported to cause infertility in cattle. The role of phytoestrogens in causing infertility is mainly recognized by accompanying signs of estrogenism including mammary development, swelling of the vulva and enlargement of the uterus [4]. Many cows suffer behavioral abnormalities such as irregular estrus, nymphomania and even anestrus [5]. Cows fail to conceive from servicing. These data are in agreement with our previous studies showing that long term feeding of a soy diet significantly increases the mean insemination rate and causes infertility in cattle [6], modulates prostaglandin secretion and action [7,8] and inhibits LH-stimulated progesterone (P4) secret...