Lysophosphatidic acid (LPA) is a lipid messenger mediated by G protein-coupled receptors (LPAR1-6). It is involved in the pathogenesis of certain chronic inflammatory and autoimmune diseases. In addition, it controls the self-renewal and differentiation of stem cells. Recent research has demonstrated the close relationship between periodontitis and various diseases in the human body. However, the precise role of LPA in the development of periodontitis has not been studied. We identified that LPAR1 was highly expressed in human periodontal ligament stem cells (PDLSCs). In periodontitis-mimicking conditions with Porphyromonas gingivalis -derived lipopolysaccharide (Pg-LPS) treatment, PDLSCs exhibited a considerable reduction in the cellular viability and osteogenic differentiation potential, in addition to an increase in the inflammatory responses including tumor necrosis factor-α and interleukin-1β expression and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Of the various LPAR antagonists, pre-treatment with AM095, an LPAR1 inhibitor, showed a positive effect on the restoration of cellular viability and osteogenic differentiation, accompanied by a decrease in NF-κB signaling, and action against Pg-LPS. These findings suggest that the modulation of LPAR1 activity will assist in checking the progression of periodontitis and in its treatment.

Lysophosphatidic acid (LPA) is an important signaling molecule. Here, the effect and mechanism of LPA on the preimplantation development of porcine embryos during in vitro culture (IVC) was examined. Porcine embryos were cultured in porcine zygote medium (PZM-3) supplemented with 30 μM LPA during different days. There was a significantly higher cleavage rate in Day 1-7 and significantly higher total cell number of blastocysts in Day 1-3 and Day 4-7. It was also found that messenger RNA (mRNA) expression level of PCNA, BCL2 and BAX in blastocysts obtained from D1-7 group were significantly higher and BCL2/BAX mRNA ratio in D1-3 group was significantly lower than control group but Day 4-7 and Day 1-7 groups were comparable with control group. Treatment with 20 μM PLC inhibitor significantly decreased the embryo cleavage rate and blastocyst formation rate. Moreover, LPA as an activator of PLCs, enhanced the 30 μM LPA + 20 μM U73122 group embryo cleavage rate which similar with control group. In conclusion, the results suggest that treatment with LPA during IVC improves the porcine early embryo cleavage by activation of PLC signaling pathway and regulate the mRNA expression that contribute to total cell number of blastocysts during blastocyst formation.

Lysophosphatidic acid (LPA) is an important signaling molecule which mediates many different cellular responses. The purpose of this study was to investigate the effect of in vitro culture (IVC) medium supplemented with LPA on the preimplantation embryonic development of porcine embryos derived from in vitro fertilization (IVF). Embryos derived from IVF were cultured in PZM-3 medium supplemented with 30 μM LPA on Day 1 to Day 7, Day 1 to Day 3 (early stage), or Day 4 to Day 7 (late stage), or without LPA. Moreover, the messenger RNA (mRNA) expression of obtaining blastocysts from each group were analyzed. Data were analyzed by ANOVA followed by Duncan using SPSS (Statistical Package for Social Science) mean ± SEM. There was a significantly higher cleavage rate in Day 1 to Day 7 than control (71.25% and 57.46%, respectively) and significantly higher total cell number of blastocysts in Day 1 to Day 3 and Day 4 to Day 7 than control (56.07,56.53 and 45.19, respectively). The results also showed that the mRNA expression level of PCNA, Bcl-2 and Bax in Day 1 to Day 7 group blastocysts were significantly higher than control and the expression level of Bax in Day 1 to Day 3 was also significantly higher than control. Moreover, it also showed that Bcl-2/Bax mRNA ratio in D1-3 group was significantly lower than control but D4-7 and D1-7 groups were comparable to control group. In conclusion, our results suggest that treatment with 30 μM LPA during IVC improves the porcine early embryo cleavage and the blastocyst total cell number after IVF and regulating the mRNA expression of blastocysts during blastocyst formation.

Lysophosphatidic acid (LPA) is a member of the phospholipid autacoid family and has growth factor and hormone-like activities on various animal cells. In this study, we investigated the effect of LPA on porcine embryo development. Porcine parthenogenetic embryos were treated into various concentrations of 0 (control), 0.1, 1 and 10 μM LPA (0 LPA, 0.1 LPA, 1 LPA and 10 LPA) during in vitro culture for 7 days or cultured in basic culture medium until day 4 and treated LPA from day 4 to day 7. In the LPA treatment for culturing from day 0 to day 7, there was no significant difference on cleavage and blastocyst formation rate. In addition, the blastocyst development proportion which was classified as expanded, hatching, or hatched blastocystshas was no significant difference among all groups. In the LPA treatment for culturing from day 4 to day 7, 0.1 and 1 LPA groups were presented increased blastocyst formation compared to other groups, but cleavage rate and over-expanded blastocyst formation rate were not significantly different among all LPA treated groups. The total cell number was not different but apoptosis was reduced when 1 LPA treated from day 4 to day 7. The relative mRNA expression level of anti-apoptosis gene, BCL2L1 was higher and pro-apoptosis gene, BAK was lower in the 1 LPA treated group than the control. In comparison with the control and the 1 LPA treated group using time-lapse monitoring system, 1 LPA treated embryo was accelerated developmental speed via morula compaction and expanded blastocyst. The 1 LPA treated group significantly increased the relative expression levels of gap junction and tight junction related genes, GJD1, CDH1 and ZO-1 compared to the control. These results indicated that 1 μM LPA supplementation for culturing from day 4 to day 7 post activation is efficient in blastocyst formation and LPA may be helpful for embryo developmental capacity.

Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator implicated in diverse biological actions, acts through the specific G-protein coupled receptors, LPA receptor (LPAR) 1～5. Our previous study showed that LPAR3 is expressed in the uterine endometrium in a cell type- and stage-specific manner and LPA via LPAR3 increases PTGS2 expression in the uterine endometrium during the period of implantation. Although LPAR3 is considered to be predominant LPA receptor in the uterine endometrium, other LPA receptors might play a role to mediate LPA functions in the uterine endometrium during pregnancy. Among LPARs, we investigated expression of LPAR1 during the estrous cycle and pregnancy in this study. Uterine endometrial tissue samples were collected from day (D) 12 and D15 of the estrous cycle and from D12, D15, D30, D60, D90 and D114 of pregnancy. Northern blot analysis determined that LPAR1 mRNA was constitutively expressed in the uterine endometrial tissues during the estrous cycle and pregnancy of all stages. Analysis by immunoblotting revealed that LPAR1 proteins were present in the porcine uterine endometrium during the estrous cycle and pregnancy. Immunohistochemical experiments demonstrated that LPAR1 protein was localized to endometrial epithelium and stromal cell, specifically to nuclei of these cell types. Results in this study show that LPAR1 is constitutively expressed in the uterine endometrium during the estrous cycle and pregnancy. These results suggest that LPA via LPAR1 may play a role in the uterine endometrial function throughout pregnancy in pigs.