Deletion of Pdcd5 in mice led to the deficiency of placenta development and embryonic lethality
Deletion of Pdcd5 in mice led to the deficiency of placenta development and embryonic lethality
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小鼠Pdcd5缺失导致胎盘发育缺陷和胚胎致死
DOI：
10.1038/cddis.2017.124
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发表时间：
2017-05-01
影响因子：
9
通讯作者：
Chen, Yingyu
中科院分区：
文献类型：
--
作者：
Li, Ge;Xu, Chentong;Chen, Yingyu
程序性细胞死亡蛋白5（PDCD5）是一种促凋亡分子，具有多种生物学活性。然而，PDCD5在体内的功能尚未得到研究。在此，我们构建了Pdcd5基因敲除小鼠模型，以研究PDCD5在体内的生理作用。Pdcd5基因敲除导致小鼠胚胎在妊娠中期致死。组织病理学分析显示，Pdcd5基因敲除（Pdcd5 - / - ）小鼠胎盘的迷路层（LZs）和交界区（JZs）发育异常，海绵滋养层细胞和滋养层巨细胞存在缺陷。此外，Pdcd5 - / - 胚胎的胎盘转运能力受损。我们还发现，Pdcd5 - / - 胚胎表现出心脏异常和肝脏发育缺陷。这种生长缺陷与胎盘发育受损有关，可能是由于胎盘氧气和营养物质转运不足所致。这些发现通过体外培养的Pdcd5基因敲除小鼠胚胎成纤维细胞得到验证，这些细胞显示出凋亡增加和G0 / G1期细胞周期阻滞。Pdcd5基因敲除降低了血管内皮生长因子（Vegf）和肝细胞生长因子（Hgf）水平，下调了下游Pik3ca - Akt - Mtor信号通路，降低了细胞存活率。总之，我们的研究表明，小鼠胚胎中Pdcd5基因敲除会导致胎盘缺陷和胚胎致死。
Programmed cell death 5 (PDCD5) is an apoptosis promoter molecule that displays multiple biological activities. However, the function of PDCD5 in vivo has not yet been investigated. Here, we generated a Pdcd5 knockout mouse model to study the physiological role of PDCD5 in vivo. Knockout of the Pdcd5 gene resulted in embryonic lethality at mid-gestation. Histopathological analysis revealed dysplasia in both the LZs and JZs in Pdcd5(-/-) placentas with defects in spongiotrophoblasts and trophoblast giant cells. Furthermore, Pdcd5(-/-) embryos had impaired transplacental passage capacity. We also found that Pdcd5(-/-) embryos exhibited cardiac abnormalities and defective liver development. The growth defect is linked to impaired placental development and may be caused by insufficient oxygen and nutrient transfer across the placenta. These findings were verified in vitro in Pdcd5 knockout mouse embryonic fibroblasts, which showed increased apoptosis and G0/G1 phase cell cycle arrest. Pdcd5 knockout decreased the Vegf and hepatocyte growth factor (Hgf) levels, downregulated the downstream Pik3ca-Akt-Mtor signal pathway and decreased cell survival. Collectively, our studies demonstrated that Pdcd5 knockout in mouse embryos results in placental defects and embryonic lethality.