Analysis of Lysophosphatidic Acid (LPA) Receptor and LPA-Induced Endometrial Prostaglandin-Endoperoxide Synthase 2 Expression in the Porcine Uterus

Abstract

Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator with diverse biological actions, acts through the specific G protein-coupled receptors endothelial differentiation gene (EDG) 2, EDG4, EDG7, and GPR23. Recent studies indicate a critical role for LPA receptor signaling in embryo implantation. To understand how LPA acts in the uterus during pregnancy in pigs, we evaluated: 1) spatial and temporal expression of LPA receptors in the uterine endometrium during the estrous cycle and pregnancy and in early-stage concepti, 2) LPA levels in uterine luminal fluids from d 12 of the estrous cycle and pregnancy, 3) effects of steroid hormones on EDG7 mRNA levels, and 4) effects of LPA on prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in the uterine endometrium using explant cultures. Of the four receptors, EDG7 was dominant, and its expression was regulated by pregnancy stage and status. EDG7 expression was highest on d 12 pregnancy, and localized to the luminal and glandular epithelium, and EDG7 mRNA levels were elevated by estrogen in the endometrium. EDG7 expression was also detected in concepti of d 12 and 15. LPA with various fatty acyl groups was present in the uterine lumen on d 12 of both the estrous cycle and pregnancy. LPA increased PTGS2 mRNA abundance in the uterine endometrium. These results indicate that LPA produced in the uterine endometrium may play a critical role in uterine endometrial function and conceptus development through EDG7-mediated PTGS2 expression during implantation and establishment of pregnancy in pigs.

Comparative aspects of implantation

“…Expression of PGE 2 synthase by trophoblast and endometrium decreases production of PGF in favor of PGE 2 to support CL maintenance (Ziecik et al 2008). In addition, LPA increases in uterine luminal fluids and endometrium of pigs in response to estrogens, binds to its receptor, EDG7, in pig conceptuses (So et al 2008), and may be critical for migration and spacing of blastocysts prior to implantation in pigs as has been reported for mice (Ye et al 2005).…”

“…High levels of IFNG may act on uterine stroma and GE to increase intracellular interferon-stimulated gene factor 3 (ISGF3) that permits lower levels of IFND to maximally upregulate STAT1 expression in close proximity to the implanting pig conceptus. To date, a limited number of estrogen-and IFN-stimulated genes have been localized in pig endometrium (see Hicks et al 2003, White et al 2005, Joyce et al 2007a, 2007b, Ka et al 2007, Ross et al 2007, So et al 2008, Song et al 2009). Type I and type II IFNs each induce expression of largely nonoverlapping sets of genes and they may also have synergistic interactions to affect physiological responses (see Levy et al 1990).…”

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

“…Lysophosphatidic acid (LPA) is a phospholipid-derived mediator increasing endometrial PTGS2 expression (Seo et al 2008; Fig. 1).…”

“…LPAR3 mRNA content is greater in the porcine endometrium from the gravid compared with the nongravid uterine horn in unilateral pregnancy ). This receptor is localized to LE, GE, and the conceptus and its expression is stimulated by estrogen (Seo et al 2008).…”

Participation of analogues of lysophosphatidic acid (LPA): oleoyl-sn-glycero-3-phosphate (L-α-LPA) and 1-oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT) in uterine smooth muscle contractility of the pregnant pigs

“…In the present study we investigated whether LPA and its analogues participate in the uterine contraction in gilts in early pregnancy. Considering the fact that in the porcine uterus the transcripts for LPA 1 and LPA 2 were also identified (Seo et al 2008), we studied whether these isoforms may participatate in action of LPA on the porcine uterus contraction activity.…”