Lysophosphatidic Acid Signaling during Embryo Development in Sheep: Involvement in Prostaglandin Synthesis

Abstract

We investigated the lysophosphatidic acid (LPA) pathway during early pregnancy in sheep. LPA was detected in the uteri of early-stage pregnant ewes. Using quantitative RT-PCR, the expression of autotaxin, the LPA-generating enzyme, was found in the endometrium and conceptus. In the latter autotaxin, transcript levels were low on d 12-14 and increased on d 15-16, in parallel with the level of LPA. Autotaxin was localized in the luminal epithelium and superficial glands of the endometrium and in trophectoderm cells of the conceptus. The expression of G protein-coupled receptors for LPA was also examined in the ovine conceptus. LPA receptor LPAR1 and LPAR3 transcripts were expressed during early pregnancy and displayed a peak on d 14, whereas the highest level of protein for both receptors was observed at d 17. LPAR1 was localized in cellular membranes and nuclear compartments of the trophectoderm cells, whereas LPAR3 was revealed only in membranes. LPA activated phosphorylation of the MAPK ERK1/2 in ovine trophectoderm-derived cells. Moreover, the bioactive lipid increased the proliferation of trophectoderm cells in culture, as shown by thymidine and bromodeoxyuridine incorporation. Furthermore, LPA induced changes to the organization of beta-actin and alpha-tubulin, suggesting a role for it in rearrangement of trophectoderm cells cytoskeleton. Because a link had previously been established between prostaglandin and LPA pathways, we analyzed the effect of LPA on prostaglandin synthesis. LPA induced an increase in the release of prostaglandin F2alpha and prostaglandin E2, with no significant modifications to cytosolic phospholipase A2alpha and prostaglandin synthase-2 expression. Taken together, our results suggest a new role for LPA-mediated signaling in the ovine conceptus at the time of implantation.

Autotaxin–lysophosphatidic acid– LPA 3 signaling at the embryo‐epithelial boundary controls decidualization pathways

“…Indeed, in mouse, sheep, pig and human, LPA 3 was expressed in the uterine epithelial layer in a female sex hormone‐dependent manner (Hama et al , 2006; Kamińska et al , 2008; Liszewska et al , 2012; Guo et al , 2013). In addition, ATX and LPA were detected in the reproductive biological fluids such as follicular fluids and uterine luminal fluids (Liszewska et al , 2009; Seo et al , 2012; Yamamoto et al , 2016). Thus, LPA 3 appears to regulate the female reproductive systems in wide range of mammalian species including human, although there are some slight differences in the process of decidualization between species (Cha et al , 2012).…”

Lysophosphatic Acid Modulates Prostaglandin Secretion in the Bovine Endometrial Cells Differently on Days 8-10 of the Estrous Cycle and Early Pregnancy

“…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 autocrine and/or paracine roles in the uterus and serve as an important factor in maintenance of early pregnancy not only in the mouse [9], pig [10,11] and sheep [12], but also in the cow [13].…”

“…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 autocrine and/or paracine roles in the uterus and serve as an important factor in maintenance of early pregnancy not only in the mouse [9], pig [10,11] and sheep [12], but also in the cow [13].In ruminants, like in many other mammals, establishment of pregnancy involves maternal recognition of pregnancy and implantation. There is much evidence showing that the maternal recognition of pregnancy in ruminants requires that the conceptus elongate from a spherical to tubular and then filamentous form to produce interferon tau (IFNτ), which is the pregnancy recognition signal that prevents development of the endometrial luteolytic mechanism [14,15].…”

“…Prostaglandin F2α is the major luteolytic agent, whereas PGE2 acts in a luteotropic and luteoprotective way and leads to elongation of the lifespan of the CL and P4 production [28,31]. It has been shown that LPA can influence on PG synthesis in mice [9], humans [32][33][34], sheep [12] and cows [13]. Therefore, the aim of this study was to determine whether LPA regulates PG synthesis and secretion in bovine endometrial cells on days 8-10 of early pregnancy compared with the respective days of the estrous cycle and which enzymes are responsible for this action within the bovine uterus.…”

Lysophosphatidic Acid Action During Early Pregnancy in the Cow: In Vivo and In Vitro Studies

“…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].…”