Lysophosphatidic Acid Action in the Bovine Corpus Luteum -An <i>In Vitro</i> Study

Abstract

Abstract. We examined whether the CL is a site for lysophosphatidic acid (LPA) synthesis and/or a target for LPA action in the bovine reproductive tract. LPA concentrations in the CL tissue increased towards the end of the cycle and were stable during early pregnancy. No changes in the expression of LPA receptors (LPARs) occurred during the estrous cycle. The expressions of LPAR2 and LPAR4 on days 17-19 of pregnancy were higher than those on the respective days of the estrous cycle and higher than those on days 8-10 of pregnancy. LPA stimulated P4 synthesis via 3βHSD stimulation but did not modulate the interferon-tau (IFNτ) influence on P4 synthesis in steroidogenic cells. Moreover, we found LPA-dependent stimulation of IFNτ action on 2,5'-oligoadenylate synthase (OAS1) and ubiquitin-like IFN-stimulated gene 15-kDa protein (ISG15) expression. The present study demonstrated that the CL might be a site of LPA synthesis and target of LPA action in the bovine reproductive tract. We postulate that during the estrous cycle and early pregnancy, LPA exerts autocrine and paracrine effects on the CL mainly via LPAR2 and LPAR4. The stimulatory effect of LPA on P4 synthesis via 3βHSD stimulation and LPA-dependent stimulation of IFNτ action on OAS1 and ISG15 expression suggest that LPA is an additional auxiliary luteosupportive factor in steroidogenic cells. T he corpus luteum (CL) is an endocrine gland that is temporarily formed in the ovary and undergoes regression at the end of the estrous cycle [1]. After ovulation, it forms from the Graafian follicle, grows and vascularizes rapidly. The bovine CL consists of a variety of cell types including large and small luteal cells, endothelial cells, fibroblasts and immune cells [2,3]. In nonpregnant cows, the CL undergoes luteolysis and becomes nonfunctional around days 17-18 after ovulation [4,5]. The main function of the CL both during the cycle and pregnancy is synthesis of progesterone (P4), which plays major roles in the regulation of the length of the estrous cycle and in the implantation of the blastocyst after fertilization [6]. During maternal recognition of pregnancy, the conceptus synthesizes and secretes interferon tau (IFNτ), which protects the CL and extends the estrous cycle [7]. In addition to its antiluteolytic effects, IFNτ increases expression of several IFN-stimulated genes (ISG), such as 2',5'-oligoadenylate synthetase (OAS1) and ubiquitin-like IFNstimulated gene 15-kDa protein (ISG15) in the uterus [8], mammary gland and CL [9] in cattle. However, during maternal recognition of pregnancy, P4 is the main factor responsible for its successful establishment. Luteinizing hormone (LH) is the most important regulator of P4 synthesis [10,11]. The growth and development of the early CL is supported by many factors, including LH, PGs (PGE 2 and PGI 2 ), oxytocin, noradrenaline and growth factors [12][13][14][15]. The CL can also autoregulate the synthesis of P4 [16].Lysophosphatidic acid (LPA) has been shown to affect the reproductive processes in rats [17], pigs [1...

Influence of Lysophosphatidic Acid on Nitric Oxide-Induced Luteolysis in Steroidogenic Luteal Cells in Cows1

“…Recently, we demonstrated the presence of LPA and its G protein-coupled receptors (GPCRs-LPARs) in bovine luteal tissue [20]. Furthermore, LPA stimulated P4 synthesis by enhancing 3bHSD expression and IFNs-dependent stimulation of gene expression in steroidogenic cells from Days 8-12 of the estrous cycle [20].…”

“…Recently, we demonstrated the presence of LPA and its G protein-coupled receptors (GPCRs-LPARs) in bovine luteal tissue [20]. Furthermore, LPA stimulated P4 synthesis by enhancing 3bHSD expression and IFNs-dependent stimulation of gene expression in steroidogenic cells from Days 8-12 of the estrous cycle [20]. Although LPA maintains P4 synthesis and action in the bovine CL in vitro [20], the modulatory role of LPA in the process of functional and structural regression of the CL controlled by NO has not been determined.…”

“…In our previous study, we found a stimulatory effect of LPA on P4 synthesis and interferon (IFN)s action in the steroidogenic cells of the bovine CL [20]. We also found that infusion of heifers with LPA prevented spontaneous luteolysis, prolonged the functional life span of the CL, and also stimulated luteotropic PGE 2 synthesis in vivo [21].…”

“…After the culture for 24 h, steroidogenic cells were exposed to an LPA agonist (1 oleoyl-sn-glycero-3-lysophosphatidic acid sodium salt [LPA]; 10 À6 M; #Alx 300-139-M005; Alexis), NO donor (NONOate; 10 À4 M; #82150; Cayman Chemical), and LPA þ NO donor for 6 h (mRNA evaluation) and 12 h (measurement of protein and P4 concentrations). The appropriate dose of LPA agonist was defined previously [20]. After incubation, the conditioned media were collected and frozen at À208C until measurement of P4 by an enzyme immunoassay (EIA) as previously described [26].…”

“…Lysophosphatidic acid (LPA) is a simple lipid that is locally produced and released from the bovine CL [20]. In our previous study, we found a stimulatory effect of LPA on P4 synthesis and interferon (IFN)s action in the steroidogenic cells of the bovine CL [20].…”