Lysophosphatidic acid increases the production of pivotal mediators of decidualization and vascularization.

BELTRAME JIMENA; SORDELLI MICAELA; CELLA MAXIMILIANO; PEREZ MARTINEZ, SILVINA; FRANCHI ANA M; RIBEIRO MARÍA LAURA

Mar del plata

Congreso; VI Latin American Symposium on Maternal-Fetal Interaction and Placenta (SLIMP) and V Latin American Symposium on Reproductive Immunology Meeting (LASRI).; 2015

SLIMP

Although the human population is incontinuous growth and will probablyreach nine billion people by 2016, global statistics indicate that 15% of couples have infertility problems. This rate is compounded considering that only 50-60% of pregnancies exceeds 20 weeks of gestation,being implantation failure the cause ofpregnancy loss in 75 % of cases.The decidualreaction and the formation of new vessels in the uterus are two crucial processesduring embryo implantation. Based on published data we postulate that lysophosphatidicacid (LPA) might be a lipid promoter of vascularization and decidualization.Previously, we observed that the pharmacological blockade of LPA3, an LPAreceptor, provoked aberrant embryo spacing and increased embryo resorption withnegative consequences in the vascularization and decidualization reactions atthe sites of embryo implantation. Thus, we investigated LPA3 potential signalingpathways. Both cyclooxygenase (COX) and nitric oxide synthase (NOS) areknown enzymes involved in implantation. Uterine slices on day 5 of gestation(day of implantation) were isolated and incubated withLPA, DGPP (a highly selective antagonistof LPA3) and COX and NOS selective and non-selective inhibitors.. We observed that LPA,through the activation of LPA3 receptor,increased inducible NOS activity and theproduction of COX-2 derived prostaglandin E2. In addition, nitric oxide and prostaglandinspresented a crosstalk under the effect of LPA. LPA also induced theexpression of markers of vascularization(IL-10) and decidualization(IGFBP-1) through LPA3 receptor and these signalingpathways involved iNOS and COX-2.Taking intoaccount our previous data, the in vitro results suggest that the LPA3 receptorand its ligand, LPA, are involved in the process ofvascularization and decidualizationthat take place duringembryo implantation.