HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 74/3/569    most recent biolreprod.105.046714v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Skaznik-Wikiel, M. E. Articles by Pru, J. K. Search for Related Content PubMed PubMed Citation Articles by Skaznik-Wikiel, M. E. Articles by Pru, J. K. Agricola Articles by Skaznik-Wikiel, M. E. Articles by Pru, J. K.

Sphingosine-1-Phosphate Receptor Expression and Signaling Correlate with Uterine Prostaglandin-Endoperoxide Synthase 2 Expression and Angiogenesis During Early Pregnancy¹

Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, and Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02114

ABSTRACT

Signaling mechanisms coordinating uterine angiogenesis and tissue remodeling during decidualization are not completely understood. Prostanoid signaling is thought to play a functionally important role in each of these events. In the present study, we demonstrate that the subfamily of G-protein-coupled receptors that binds and becomes activated by the terminal signaling lipid in the sphingolipid pathway, sphingosine-1-phosphate (S1P), were expressed during uterine decidualization. Three of the five known S1P receptors, termed endothelial differentiation genes (Edg; Edg1, Edg3, and Edg5) were upregulated in the uterine deciduum from Day of Pregnancy (DOP) 4.5 to 7.5, while Edg6 and Edg8 expression remained unchanged. Consistent with angiogenesis in general during decidualization, we believe EDG1 and EDG5 to be regulated by the embryo because no microvascular expression for these receptors was observed in oil-induced deciduomas. Observed expression of EDG1 and EDG5 showed a similar expression pattern to that previously reported for prostaglandin-endoperoxide synthase 2 (PTGS2), transitioning from the sublumenal stromal compartment in the antimesometrial pole (DOP 5) to the microvasculature of the mesometrial pole (DOP 7). Furthermore, these two receptors colocalized with PTGS2 at three additional sites at the maternal:fetal interface throughout pregnancy. Treatment of cultured predecidualized stromal cells with S1P resulted in upregulation of Ptgs2 mRNA and PTGS2 protein, but not the downstream enzyme prostacyclin synthase. These combined results suggest the existence of a link between the sphingolipid and prostanoid signaling pathways in uterine physiology, and that, based on their expression pattern, S1P receptors function to coordinate uterine mesometrial angiogenesis during the implantation phase of early gestation.

angiogenesis, cyclooxygenase-2, decidua, developmental biology, G-protein-coupled receptor, implantation, pregnancy, signal transduction, sphingosine-1-phosphate, uterus

² Correspondence: James K. Pru, Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Room 6613B, Building 149, 149 13th Street, Charlestown, MA 02129. FAX: 617 724 9935; jpru{at}partners.org

¹ Supported in part by Vincent Memorial Research Funds and NIH Grant R01-ES012070 to J.K.P.

This article has been cited by other articles:

				X. Ye Lysophospholipid signaling in the function and pathology of the reproductive system Hum. Reprod. Update, September 1, 2008; 14(5): 519 - 536. [Abstract] [Full Text] [PDF]

				T. Kaneko-Tarui, L. Zhang, K. J Austin, L. E Henkes, J. Johnson, T. R Hansen, and J. K Pru Maternal and Embryonic Control of Uterine Sphingolipid-Metabolizing Enzymes During Murine Embryo Implantation Biol Reprod, October 1, 2007; 77(4): 658 - 665. [Abstract] [Full Text] [PDF]

				Y.-J. Jeng, V. R. Suarez, M. G. Izban, H.-Q. Wang, and M. S. Soloff Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1110 - E1121. [Abstract] [Full Text] [PDF]