Oefner C M, Sharkey A, Gardner L, Critchley H, Oyen M, Moffett A
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Placenta. 2015 Jan;36(1):59-68. doi: 10.1016/j.placenta.2014.10.012. Epub 2014 Nov 1.
Extracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear.
Immunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle was determined by qPCR and protein localisation by immunohistochemistry. The structure of col-IV in placenta was examined using transmission electron microscopy. Finally, the expression of col-IV alpha chain NC1 domains and collagen receptors was localised by immunohistochemistry.
Col-IV alpha chains were selectively up-regulated during the menstrual cycle and decidualisation. Primary extravillous trophoblast cells express collagen receptors and secrete col-IV in vitro and in vivo, resulting in the increased levels found in decidua basalis compared to decidua parietalis. A novel expression pattern of col-IV in the mesenchyme of placental villi, as a three-dimensional network, was found. NC1 domains of col-IV alpha chains are known to regulate tumour cell migration and the selective expression of these domains in decidua basalis compared to decidua parietalis was determined.
Col-IV is expressed as novel forms in the placenta. These findings suggest that col-IV not only represents a structural protein providing tissue integrity but also influences the invasive behaviour of trophoblast cells at the implantation site.
细胞外基质蛋白在影响滋养层细胞侵袭方面起着关键作用。然而，胶原蛋白尤其是IV型胶原蛋白（col-IV）在着床部位的作用尚不清楚。
采用免疫组织化学法确定月经周期和妊娠早期子宫内膜和蜕膜中I、III、IV和VI型胶原蛋白的分布。通过qPCR测定生殖周期中col-IVα链的表达，并通过免疫组织化学确定蛋白定位。使用透射电子显微镜检查胎盘组织中col-IV的结构。最后，通过免疫组织化学对col-IVα链NC1结构域和胶原蛋白受体的表达进行定位。
在月经周期和蜕膜化过程中，col-IVα链选择性上调。原代绒毛外滋养层细胞在体外和体内均表达胶原蛋白受体并分泌col-IV，导致与壁蜕膜相比，基蜕膜中col-IV水平升高。发现col-IV在胎盘绒毛间充质中呈现一种新的三维网络表达模式。已知col-IVα链的NC1结构域可调节肿瘤细胞迁移，并确定了这些结构域在基蜕膜与壁蜕膜中的选择性表达。
col-IV在胎盘中以新的形式表达。这些发现表明，col-IV不仅是一种提供组织完整性的结构蛋白，还影响着床部位滋养层细胞的侵袭行为。
