@article{3bce6c3175a144a0a81536e2b94567ce,
title = "Autotaxin–lysophosphatidic acid–LPA3 signaling at the embryo-epithelial boundary controls decidualization pathways",
abstract = "During pregnancy, up-regulation of heparin-binding (HB-) EGF and cyclooxygenase-2 (COX-2) in the uterine epithelium contributes to decidualization, a series of uterine morphological changes required for placental formation and fetal development. Here, we report a key role for the lipid mediator lysophosphatidic acid (LPA) in decidualization, acting through its G-protein-coupled receptor LPA3 in the uterine epithelium. Knockout of Lpar3 or inhibition of the LPA-producing enzyme autotaxin (ATX) in pregnant mice leads to HB-EGF and COX-2 down-regulation near embryos and attenuates decidual reactions. Conversely, selective pharmacological activation of LPA3 induces decidualization via up-regulation of HB-EGF and COX-2. ATX and its substrate lysophosphatidylcholine can be detected in the uterine epithelium and in pre-implantation-stage embryos, respectively. Our results indicate that ATX–LPA–LPA3 signaling at the embryo-epithelial boundary induces decidualization via the canonical HB-EGF and COX-2 pathways.",
keywords = "LPA, autotaxin, decidualization, embryo implantation, lysophosphatidic acid",
author = "Shizu Aikawa and Kuniyuki Kano and Asuka Inoue and Jiao Wang and Daisuke Saigusa and Takeshi Nagamatsu and Yasushi Hirota and Tomoyuki Fujii and Soken Tsuchiya and Yoshitaka Taketomi and Yukihiko Sugimoto and Makoto Murakami and Makoto Arita and Makoto Kurano and Hitoshi Ikeda and Yutaka Yatomi and Jerold Chun and Junken Aoki",
note = "Funding Information: We thank Shionogi pharmaceutical Co., Ltd for the gift of the ATX inhibitor. We also thank Dr Yasumasa Nishito (Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science) for DNA microarray analysis. The present work was supported partly by AMED-CREST (Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology) for J.A. and M.M., PRESTO (Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology) for A.I., Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Scientific Research for J.A. and M.M. Publisher Copyright: {\textcopyright} 2017 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2017",
month = jul,
day = "14",
doi = "10.15252/embj.201696290",
language = "English",
volume = "36",
pages = "2146--2160",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "14",
}