Nuclear Localisation of the Endocannabinoid Metabolizing Enzyme Fatty Acid Amide Hydrolase (FAAH) in Invasive Trophoblasts and an Association with Recurrent Miscarriage
Nuclear Localisation of the Endocannabinoid Metabolizing Enzyme Fatty Acid Amide Hydrolase (FAAH) in Invasive Trophoblasts and an Association with Recurrent Miscarriage
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DOI：
10.1016/j.placenta.2008.08.003
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发表时间：
2008-11-01
期刊：
影响因子：
3.8
通讯作者：
Glass, M.
中科院分区：
文献类型：
--
作者：
Chamley, L. W.;Bhalla, A.;Glass, M.
内源性大麻素是一种脂质信号分子，与大麻中的主要精神活性成分--β-四氢大麻酚有关，在早期胚胎的植入和发育中发挥着越来越重要的作用。内源性大麻酰胺是由脂肪酸酰胺水解酶(FAAH)代谢的，这种酶的水平不足与妇女自然流产和小鼠着床失败有关。我们用免疫组织化学方法筛选了45例反复流产妇女和17例妊娠匹配的正常妊娠妇女胎盘床活检和胎盘组织中FAAH的表达。出乎意料的是，该酶似乎定位于滋养层细胞核，亚细胞组分的Western blotting和共聚焦显微镜证实了这一点。FAAH在大蜕膜基质细胞胞浆中表达，反复流产组(73%)明显高于正常妊娠组(31%)。FAAH也表达于侵袭蜕膜的绒毛外滋养层细胞核，在67%的反复流产患者中未见表达，而在正常妊娠的患者中未见表达。相反，FAAH在绒毛外滋养细胞中表达，这些滋养细胞已经从绒毛中迁移出来，但在正常妊娠和反复流产的病例中尚未侵入蜕膜。FAAH在一些标本的绒毛滋养层细胞核中也有表达，FAAH在侵入蜕膜的滋养层细胞以及在许多反复流产的大蜕膜基质细胞中呈过度表达。这可能反映了对反复流产的妇女子宫中大麻素系统的控制不足。FAAH在滋养层细胞中意外的核定位的功能意义尚不清楚。(C)2008爱思唯尔有限公司。保留所有权利。
Endocannabiniods are lipid signalling molecules that are related to the major psychoactive component in marijuana, delta-9-tetrahydrocannabinol and are increasingly recognized as being important in implantation and development of early embryos. The endocannabinoid anandamide, is metabolized by the enzyme fatty acid amide hydrolase (FAAH), and insufficient levels of this enzyme have been implicated in spontaneous miscarriage in women and implantation failure in mice.We screened placental bed biopsies and placental tissue from 45 women with recurrent miscarriage and 17 gestation-matched women with normal pregnancies for the expression of FAAH by immunohistochemistry. Unexpectedly, the enzyme appeared to be localised to the nucleus of trophoblasts and this was confirmed by western blotting of sub-cellular fractions and confocal microscopy. FAAH was expressed in the cytoplasm of large decidual stromal cells and significantly more women with recurrent miscarriage (73%) expressed FAAH in these cells than women with normal pregnancy (31%). FAAH was also expressed in the nucleus of extravillous trophoblasts that had invaded the decidua from 67% of women with recurrent miscarriage but was not expressed by these cells in any women with normal pregnancies. In contrast, FAAH was expressed in extravillous trophoblasts that had Migrated Out of the villi but that had not yet invaded the decidua in both normal pregnancies and in cases of recurrent miscarriage. FAAH was also present in the nucleus of a small number Of villous trophoblasts in some specimens.FAAH appears to be over expressed in trophoblasts that have invaded the decidua, as well as in large decidual stromal cells in many cases of recurrent miscarriage. This May reflect inadequate control of the cannabinoid system in the uterus of women who experience recurrent Miscarriages. The functional significance of the unexpected nuclear localisation of FAAH in trophoblasts is not yet clear. (C) 2008 Elsevier Ltd. All rights reserved.