Lysophosphatidic acid increases the production of pivotal mediators of decidualization and vascularization in the rat uterus

BELTRAME JIMENA; SORDELLI, MICAELA SOLEDAD; CELLA, MAXIMILIANO; PEREZ MARTINEZ SILVINA; FRANCHI, ANA MARIA; RIBEIRO MARIA LAURA

PLACENTA

W B SAUNDERS CO LTD

Lugar: Londres; Año: 2013 vol. 34 p. 751 - 756

0143-4004

Introduction: The decidual reaction and the formation of new vessels in the uterus are two crucialprocesses during embryo implantation. Previously, we observed that lysophosphatidic acid (LPA) increasescyclooxygenase-2 derived e prostaglandin E2 production during implantation in the rat uterusand that it augments the expression of decidualization (IGFBP-1) and vascularization (IL-10) markers.Both cyclooxygenase and nitric oxide synthase (NOS) are known enzymes involved in these processes.Thus, we became interested in studying which factors contribute to LPA receptor-specific role during thedecidual and the vascular reaction at implantation.Methods: We adopted a pharmacological approach in vitro incubating the uterus from rats on day 5 ofgestation (day of implantation) with LPA, DGPP (a highly selective antagonist of LPA3, an LPA receptor)and cyclooxygenase and NOS selective and non-selective inhibitors. We determined NOS activity,prostaglandin E2 production and IGFBP-1 and IL-10 expression to evaluate decidualization andvascularization.Results: We observed that LPA augmented the activity of the inducible NOS isoform through LPA1/LPA3.Inducible NOS activity participated in the induction of cyclooxygenase-2/prostaglandin E2 increasestimulated by LPA. Also, cyclooxygenase-2 derived prostaglandins mediated LPA-stimulatory action onNOS activity. Both cyclooxygenase-2 and inducible NOS mediated LPA effect on IGFBP-1 and IL-10expression.Conclusions: These results suggest the participation of LPA/LPA3 in the production of crucial moleculesinvolved in vascularization and decidualization, two main processes that prepare the uterine milieu forembryo invasion during implantation.