小鼠异常子宫折叠破坏着床室的形成和胚胎-子宫轴的排列

Manoj K Madhavan, F. DeMayo, J. Lydon, Niraj R. Joshi, A. Fazleabas, R. Arora
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引用次数: 3

摘要

哺乳动物(包括人、马和啮齿动物)的子宫腔上皮皱褶具有特征性。马子宫折叠不当导致妊娠失败,但折叠的确切功能尚不清楚。在这里,我们揭示了妊娠早期子宫三维折叠模式的动态变化,整个腔形成着床前沿系膜-反系膜轴的横向折叠。利用时间过程,我们发现横向褶皱是在胚胎间隔之前形成的,而着床室是在胚胎开始附着时形成的。因此,褶皱和腔室是两种不同的结构。横向折叠形成一个平坦的着床区域,之后胚胎到达其中心附着并形成着床后腔。我们的数据还表明,着床室有助于胚胎旋转及其沿子宫系膜-反系膜轴的排列。在WNT5A-和rbpj缺陷小鼠中,我们发现纵向褶皱中的胚胎表现出胚胎-子宫轴错位、腔室形成异常和着床后形态发生缺陷。这些子宫折叠破裂的小鼠模型为了解子宫结构机制提供了一个机会,这对植入和妊娠成功至关重要。这篇文章有一个相关的“报纸背后的人”采访。
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Aberrant uterine folding in mice disrupts implantation chamber formation and alignment of embryo-uterine axes
ABSTRACT The uterine luminal epithelium folds characteristically in mammals, including humans, horses and rodents. Improper uterine folding in horses results in pregnancy failure, but the precise function of folds remains unknown. Here, we uncover dynamic changes in the 3D uterine folding pattern during early pregnancy with the entire lumen forming pre-implantation transverse folds along the mesometrial-antimesometrial axis. Using a time course, we show that transverse folds are formed before embryo spacing, whereas implantation chambers form as the embryo begins attachment. Thus, folds and chambers are two distinct structures. Transverse folds resolve to form a flat implantation region, after which an embryo arrives at its center to attach and form the post-implantation chamber. Our data also suggest that the implantation chamber facilitates embryo rotation and its alignment along the uterine mesometrial-antimesometrial axis. Using WNT5A- and RBPJ-deficient mice that display aberrant folds, we show that embryos trapped in longitudinal folds display misalignment of the embryo-uterine axes, abnormal chamber formation and defective post-implantation morphogenesis. These mouse models with disrupted uterine folding provide an opportunity to understand uterine structure-based mechanisms that are crucial for implantation and pregnancy success. This article has an associated ‘The people behind the papers’ interview.
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