Inagaki Mai, Nishimura Tomohiro, Akanuma Shin-Ichi, Nakanishi Takeo, Tachikawa Masanori, Tamai Ikumi, Hosoya Ken-Ichi, Nakashima Emi, Tomi Masatoshi
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Placenta. 2017 May;53:76-82. doi: 10.1016/j.placenta.2017.04.002. Epub 2017 Apr 6.
The placenta is an organ that secretes prostaglandin (PG) E into the fetal-placental circulation to regulate both vascular tone and remodeling of the fetal ductus arteriosus. Placental PGE synthesis might be mediated by microsomal PGE synthase-1 (mPGES-1), in addition to cyclooxygenase (COX) isoforms. Thus, the purpose of this study is to clarify the temporal and spatial expression patterns of mPGES-1, together with COX-1 and COX-2, in murine placenta. We found that mPGES-1 and COX-1 protein levels continuously increased in the placental labyrinth from gestational day (GD) 13.5 to GD19.5, becoming higher than in the decidua or the junctional zone by GD17.5. The PGE level at GD17.5 was also highest in the labyrinth. Immunofluorescence stainings for mPGES-1 and COX-1 in the labyrinth at GD17.5 overlapped and were located on the fetal side of the signals for connexin 26, which forms gap junctions between maternal-facing (SynT-I) and fetal-facing (SynT-II) syncytiotrophoblast layers, and on the maternal side of the signals for glucose transporter 1 on the basal plasma membrane of SynT-II. On the other hand, the signals for COX-2 did not overlap with those for mPGES-1. These results indicate that COX-1 and mPGES-1 are co-localized in murine placental SynT-II, facing the fetal-placental circulation. Therefore, SynT-II could contribute to placental synthesis of PGE for release into the fetal-placental circulation.
胎盘是一种将前列腺素(PG)E分泌到胎儿 - 胎盘循环中以调节血管张力和胎儿动脉导管重塑的器官。除环氧化酶(COX)亚型外,胎盘PGE的合成可能由微粒体PGE合酶 - 1(mPGES - 1)介导。因此,本研究的目的是阐明mPGES - 1与COX - 1和COX - 2在小鼠胎盘中的时空表达模式。我们发现,从妊娠第(GD)13.5天到GD19.5天,胎盘迷路中mPGES - 1和COX - 1蛋白水平持续升高,到GD17.5天时高于蜕膜或交界区。GD17.5天时迷路中的PGE水平也最高。GD17.5天时迷路中mPGES - 1和COX - 1的免疫荧光染色重叠,位于连接蛋白26信号的胎儿侧,连接蛋白26在面向母体(SynT - I)和面向胎儿(SynT - II)的合体滋养层之间形成缝隙连接,并且位于SynT - II基底质膜上葡萄糖转运蛋白1信号的母体侧。另一方面,COX - 2的信号与mPGES - 1的信号不重叠。这些结果表明,COX - 1和mPGES - 1在面向胎儿 - 胎盘循环的小鼠胎盘SynT - II中共定位。因此,SynT - II可能有助于胎盘合成PGE并释放到胎儿 - 胎盘循环中。