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Trophoblast-endometrial interaction in a 3D culture system as a model for early human implantation

3D 培养系统中滋养层与子宫内膜的相互作用作为人类早期植入的模型

基本信息

批准号：
346386149
负责人：
Dr. Volker Uwe Buck
金额：
--
依托单位：
Institut für Molekulare und Zelluläre Anatomie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/346386149?language=en
关键词：
Trophoblast endometrial interaction 3D culture

项目摘要

A basic requirement for human embryo implantation, which comprises penetration of endometrial epithelial cells (EEC) by trophoblast cells, is the appropriate preparation of the endometrium. Its cyclic differentiation leads to a short receptive period called window of implantation (WOI). About 30% of all pregnancies are lost during the early implantation phase. Insights in early mechanisms of human implantation may therefore improve the success rates of assisted reproductive technologies (ART).Our goal is to unravel basic mechanisms of early human implantation by using a newly established 3D cell culture confrontation system. Previously, in a study on human endometrial tissue we observed an altered distribution of adhering junctions along lateral membranes of glandular EEC during the WOI that indicates a change in EEC polarity. In the 3D cell culture confrontation system gland-like endometrial cell line spheroids with a junction distribution similar to EEC during the WOI were more strongly invaded by the extravillous trophoblast cell line AC-1M88 than spheroids that were derived from highly polarised endometrial cell lines.In the present project we will focus on the investigation of changes in epithelial junctional complexes and the associated cytoskeleton to elucidate mechanisms of trophoblast invasion. Using the established 2D and 3D culture systems as well as primary cells both spatial and temporal aspects of trophoblast-endometrial interaction will be analysed in detail by means of immunohistology and live cell imaging. By use of light sheet microscopy we expect a particularly high resolution of the invasive processes. A further aim is to analyse the influence of 17beta-estradiol and progesterone on endometrial epithelial receptivity and on the invasiveness of trophoblast cells.We expect that the results will provide new insights into the crucial mechanisms of human implantation and thus may help to improve the outcome of ART in the future.

人胚胎植入的基本要求是子宫内膜的适当准备，其中包括滋养层细胞穿透子宫内膜上皮细胞（EEC）。它的周期性分化导致一个短暂的接受期，称为植入窗口（WOI）。大约30%的妊娠在早期着床阶段丢失。因此，对人类植入早期机制的深入了解可能会提高辅助生殖技术（ART）的成功率。我们的目标是通过使用新建立的3D细胞培养对抗系统来解开人类早期植入的基本机制。以前，在对人子宫内膜组织的研究中，我们观察到在WOI期间沿着腺EEC的侧膜的粘附连接沿着分布的改变，这表明EEC极性的变化。在3D细胞培养对抗系统中，在WOI期间具有类似于EEC的连接分布的腺体样子宫内膜细胞系球状体更强烈地被绒毛外滋养层细胞系AC-100侵袭。在本项目中，我们将重点研究上皮连接复合体和相关细胞骨架的变化，以阐明其机制滋养层细胞的入侵。使用已建立的二维和三维培养系统以及原代细胞，滋养层-子宫内膜相互作用的空间和时间方面将通过免疫组织学和活细胞成像进行详细分析。通过使用光片显微镜，我们期望侵入过程的特别高的分辨率。进一步的目的是分析17 β-雌二醇和孕酮对子宫内膜上皮细胞容受性和滋养层细胞侵袭性的影响，我们期望这些结果将为人类植入的关键机制提供新的见解，从而有助于改善ART的结果。