Characterisation of Osteopontin in an In Vitro Model of Embryo Implantation
Characterisation of Osteopontin in an In Vitro Model of Embryo Implantation
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DOI：
10.3390/cells8050432
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发表时间：
2019-05-01
期刊：
影响因子：
6
通讯作者：
Aplin, John D.
中科院分区：
文献类型：
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作者：
Berneau, Stephane C.;Ruane, Peter T.;Aplin, John D.
在怀孕开始时，胚胎着床是由子宫内膜上皮和囊胚外滋养外胚层细胞之间的相互作用启动的。骨桥蛋白（OPN）在子宫内膜中表达，并参与胚胎-上皮界面的附着和信号作用。我们使用三种不同的单克隆抗体对人子宫内膜上皮石川细胞系中的OPN进行了表征，揭示了至少九种不同的分子量形式，以及在细胞组织形成融合上皮层诱导的顶端区域的一种新的分泌途径定位。小鼠囊胚与石川细胞层共培养，模拟胚胎着床时的附着、附着和初始侵袭。外源OPN减弱了胚胎对石川细胞最初的弱附着，但不影响胚胎对石川细胞的稳定附着。值得注意的是，外源OPN抑制了底层细胞层的胚胎侵袭，这与从滋养外胚层（Gata2）向侵袭性滋养层巨细胞分化相关的转录因子的表达改变（Hand1）相对应。这些数据证明了子宫内膜OPN形式的复杂性，并表明OPN通过向滋养外胚层发出信号来调节着床时的胚胎入侵。
At the onset of pregnancy, embryo implantation is initiated by interactions between the endometrial epithelium and the outer trophectoderm cells of the blastocyst. Osteopontin (OPN) is expressed in the endometrium and is implicated in attachment and signalling roles at the embryo-epithelium interface. We have characterised OPN in the human endometrial epithelial Ishikawa cell line using three different monoclonal antibodies, revealing at least nine distinct molecular weight forms and a novel secretory pathway localisation in the apical domain induced by cell organisation into a confluent epithelial layer. Mouse blastocysts co-cultured with Ishikawa cell layers served to model embryo apposition, attachment and initial invasion at implantation. Exogenous OPN attenuated initial, weak embryo attachment to Ishikawa cells but did not affect the attainment of stable attachment. Notably, exogenous OPN inhibited embryonic invasion of the underlying cell layer, and this corresponded with altered expression of transcription factors associated with differentiation from trophectoderm (Gata2) to invasive trophoblast giant cells (Hand1). These data demonstrate the complexity of endometrial OPN forms and suggest that OPN regulates embryonic invasion at implantation by signalling to the trophectoderm.