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INRA (E.L., P.Re., O.D., G.C.), UMR 1198 Biologie du Développement et Reproduction, F-78350 Jouy en Josas, France; and Institut de Biochimie et Biophysique Moleculaire et Cellulaire (E.B.-D., P.Ro.), Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8619, Equipe Signalisation et Régulations Cellulaires, Université Paris-Sud, F-91400 Orsay, France
Address all correspondence and requests for reprints to: Gilles Charpigny, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1198 Biologie du Développement et Reproduction, F-78350 Jouy en Josas, France. E-mail: gilles.charpigny{at}jouy.inra.fr.
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 β-actin and
-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 F2
and prostaglandin E2, with no significant modifications to cytosolic phospholipase A2
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.
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