N-acylphosphatidylethanolamine-hydrolyzing phospholipase D is an important determinant of uterine anandamide levels during implantation

N-acylphosphatidylethanolamine-hydrolyzing phospholipase D is an important determinant of uterine anandamide levels during implantation
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DOI:
10.1074/jbc.c500168200
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发表时间:
2005-06-24
影响因子:
4.8
通讯作者:
Dey, SK
Dey, SK
中科院分区:
生物学2区
文献类型:
--
作者:
Guo, Y;Wang, HB;Dey, SK

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着床需要胚泡和接受性子宫之间的相互作用。在小鼠中,这种对话中的一个重要参与者涉及通过大麻素受体CB 1的内源性大麻素信号。大麻素是一种内源性大麻素配体,其水平在妊娠早期的子宫中受到时空调节,在受体子宫和着床部位显示出较低的水平。然而,在不同妊娠状态下建立不同子宫大麻素梯度的机制尚不清楚。使用多种方法,我们在这里表明,子宫花生四烯酸水平有利于植入主要受时空表达的Nape-Pld,基因编码N-酰基磷脂酰乙醇胺水解磷脂酶D,产生花生四烯酸。表达与其活性和花生四烯酸水平密切相关。这项研究具有临床意义,因为外周循环中大麻素水平升高与女性自发性妊娠失败相关。
Implantation requires reciprocal interaction between blastocysts and a receptive uterus. In mice, one important player in this dialogue involves endocannabinoid signaling via cannabinoid receptor CB1. Anandamide is an endogenous cannabinoid ligand, and its levels are spatiotemporally regulated in the uterus during early pregnancy, showing lower levels in the receptive uterus and at the implantation site. However, the mechanism by which differential uterine anandamide gradients are established under different pregnancy status is not clearly understood. Using multiple approaches, we show here that uterine anandamide levels conducive to implantation are primarily regulated by spatiotemporal expression of Nape-Pld, the gene encoding N-acylphosphatidylethanolamine-hydrolyzing phospholipase D that generates anandamide. The expression is well correlated with its activity and anandamide levels. This study is clinically relevant, since elevated anandamide levels in peripheral circulation are associated with spontaneous pregnancy failure in women.