The interface of the immune and reproductive systems in the ovary: lessons learned from the corpus luteum of domestic animal models.

The dynamic changes that characterize the female reproductive system are regulated by hormones. However, local cell-to-cell interactions may mediate responsiveness of tissues to hormonal signals. The corpus luteum (CL) is an excellent model for understanding how immune cells are recruited into tissues and the role played by those cells in regulating tissue homeostasis or demise. Leukocytes are recruited into the CL throughout its lifespan, and leukocyte-derived cytokines have been found in corpora lutea of all species examined. The proinflammatory cytokines inhibit gonadotropin-stimulated steroidogenesis, profoundly stimulate prostaglandin synthesis by luteal cells, and promote apoptosis. However, there is mounting evidence that leukocytes and luteal cells communicate in different ways to maintain homeostasis within the functional CL. Domestic animals have provided important information regarding the presence and role of immune cells in the CL.

Lysophosphatic acid modulates prostaglandin secretion in the bovine endometrial cells differently on days 8-10 of the estrous cycle and early pregnancy.

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 PGE(2) production in stromal cells during the estrous cycle and early pregnancy. On days 8-10 of pregnancy, LPA inhibited PGF(2alpha) 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 PGE(2) synthesis and mRNA expression for PGES in stromal cells. Moreover, during early pregnancy, LPA might protect bovine CL and early embryo development by decreasing PGF(2alpha) synthesis and mRNA expression for PGFS in the epithelial cells of the bovine endometrium.

Lysophosphatic acid modulates prostaglandin secretion in the bovine uterus.

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(2alpha) synthase (aldose reductase with 20 alpha-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(2)(alpha) ratio. It suggests that LPA may serve as an important factor in the maintenance of early pregnancy in cow.

Concentrations of isoflavones and their metabolites in the blood of pregnant and non-pregnant heifers fed soy bean.

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 early-pregnant 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.