Autotaxin-lysophosphatidic acid-LPA(3) signaling at the embryo-epithelial boundary controls decidualization pathways

作者：Aikawa Shizu; Kano Kuniyuki; Inoue Asuka; Wang Jiao; Saigusa Daisuke; Nagamatsu Takeshi; Hirota Yasushi; Fujii Tomoyuki; Tsuchiya Soken; Taketomi Yoshitaka; Sugimoto Yukihiko; Murakami Makoto; Arita Makoto; Kurano Makoto; Ikeda Hitoshi; Yatomi Yutaka; Chun Jerold; Aoki Junken^*

来源：The EMBO Journal, 2017, 36(14): 2146-2160.

DOI：10.15252/embj.201696290

• autotaxin
• decidualization
• embryo implantation
• LPA(3)
• lysophosphatidic acid

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 LPA(3) in the uterine epithelium. Knockout of Lpar(3) 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 LPA(3) 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-LPA(3) signaling at the embryoepithelial boundary induces decidualization via the canonical HB-EGF and COX-2 pathways.

• 出版日期2017-7-14
• 单位河北医科大学