Activation of the epithelial Na+ channel triggers prostaglandin E2 release and production required for embryo implantation
Activation of the epithelial Na+ channel triggers prostaglandin E2 release and production required for embryo implantation
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DOI：
10.1038/nm.2771
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发表时间：
2012-07-01
期刊：
影响因子：
82.9
通讯作者：
Chan, Hsiao Chang
中科院分区：
文献类型：
--
作者：
Ruan, Ye Chun;Guo, Jing Hui;Chan, Hsiao Chang
胚胎植入仍然是一个知之甚少的过程。我们在此证明，胚胎释放的丝氨酸蛋白酶胰蛋白酶激活小鼠子宫内膜上皮细胞中的上皮Na+通道（ENaC），触发Ca 2+内流，导致前列腺素E-2（PGE（2））释放、转录因子CREB磷酸化和环氧合酶2（前列腺素产生和植入所需的酶）上调（1-3）。在小鼠植入时，我们检测到最大ENaC激活，如ENaC切割所示（4）。阻断或敲低小鼠子宫ENaC导致着床失败。此外，我们发现，与成功怀孕的女性相比，着床失败的女性在体外受精（IVF）治疗前的子宫ENaC表达明显较低。这些结果表明，ENaC在调节胚胎植入所需的PGE（2）产生和释放方面的作用以前未明确，缺陷可能是流产和IVF成功率低的原因。
Embryo implantation remains a poorly understood process. We demonstrate here that activation of the epithelial Na+ channel (ENaC) in mouse endometrial epithelial cells by an embryo-released serine protease, trypsin, triggers Ca2+ influx that leads to prostaglandin E-2 (PGE(2)) release, phosphorylation of the transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation(1-3). We detected maximum ENaC activation, as indicated by ENaC cleavage(4), at the time of implantation in mice. Blocking or knocking down uterine ENaC in mice resulted in implantation failure. Furthermore, we found that uterine ENaC expression before in vitro fertilization (IVF) treatment is markedly lower in women with implantation failure as compared to those with successful pregnancy. These results indicate a previously undefined role of ENaC in regulating the PGE(2) production and release required for embryo implantation, defects that may be a cause of miscarriage and low success rates in IVF.