title: Lysophosphatidic acid and sphingosine 1-phosphate metabolic pathways and their receptors are differentially regulated during decidualization of human endometrial stromal cells.
abstract: In the luteal phase, human endometrial stromal cells (HESCs) undergo proliferation, migration and differentiation during the decidualization process under the control of the ovarian steroids progesterone and estrogen. Proper decidualization of stromal cells is required for blastocyst implantation and the development of pregnancy. The proliferation, migration and differentiation of HESCs in decidualization do not require the presence of a blastocyst but are greatly accelerated during implantation. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are potent bioactive lysophospholipids that have critical roles in various physiological and pathophysiological processes, including inflammation, angiogenesis and cancer. The expression of the enzymes involved in LPA and S1P turnover and their receptors in HESCs during decidualization has not been characterized yet. We found that the LPAR1 and LPAR6 and S1PR3 receptors are highly expressed in HESCs. LPAR1, autotaxin (ATX), an LPA producing enzyme and lipid phosphate phosphatase 3 were up-regulated during decidualization. Interestingly, the expression of all S1P receptor subtypes and LPA receptors (LPAR2-6) mRNA was down-regulated after decidualization. We found that SPHK1 is highly expressed in HESCs, and is up-regulated during decidualization. S1P phosphatase SGPP1 and S1P lyase SGPL1 are highly expressed in HESCs. SGPP1 mRNA expression was significantly up-regulated in decidualized HESCs. In conclusion, this study shows the first time that specific LPA and S1P receptors and their metabolizing enzymes are highly regulated in HESCs during decidualization. Furthermore, we suggest that LPAR1 receptor-mediated signaling in HESCs may be crucial in decidualization process. SPHK1 activity and high turnover of S1P and LPA might be essential for precise regulation of their signaling during decidualization of human endometrium and implantation.
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Ferdinand-Sauerbruchstrasse, D-17489 Greifswald, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Brünnert
authors.affiliation: Department of Biology and Pathology of Human Reproduction, Bialystok, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Sztachelska
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Ferdinand-Sauerbruchstrasse, D-17489 Greifswald, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Bornkessel
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Ferdinand-Sauerbruchstrasse, D-17489 Greifswald, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Treder
authors.affiliation: Department of Biology and Pathology of Human Reproduction, Bialystok, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Wolczynski
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Ferdinand-Sauerbruchstrasse, D-17489 Greifswald, Germany Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandar Sindri, Kishangarh, Rajasthan 305 801, India pankaj_bio@curaj.ac.in.
authors.forename: P
authors.initials: P
authors.lastname: Goyal
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Ferdinand-Sauerbruchstrasse, D-17489 Greifswald, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zygmunt
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D003656:Decidua / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000166:cytology; D004967:Estrogens; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D008875:Middle Aged; D010711:Phosphatidate Phosphatase / Q000096:biosynthesis; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis; D011247:Pregnancy; D011374:Progesterone; D012333:RNA, Messenger / Q000096:biosynthesis; D049368:Receptors, Lysophosphatidic Acid / Q000096:biosynthesis*; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D017154:Stromal Cells / Q000166:cytology; D015533:Transcriptional Activation; D015854:Up-Regulation; D000099189:Lysophospholipase D
chemical_list: D004967:Estrogens; D008246:Lysophospholipids; D010711:Phosphatidate Phosphatase; D010727:Phosphoric Diester Hydrolases; D011374:Progesterone; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000081025:Sphingosine-1-Phosphate Receptors; D000099189:Lysophospholipase D; C577483:sphingosine-1-phosphate receptor-3, human; C060506:sphingosine 1-phosphate; C112948:lipid phosphate phosphatase; C032881:lysophosphatidic acid
keywords: LPA; S1P; decidualization; endometrial stromal cells; endometrium