Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA.
Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA.
Development. 2022 Jun 1;149(11). doi: 10.1242/dev.200300. Epub 2022 Jun 13.
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.
哺乳动物（包括人类、马和啮齿动物）的子宫腔上皮会呈现出特有的折叠形态。马的子宫折叠不当会导致妊娠失败，但折叠的确切功能尚不清楚。在这里，我们揭示了整个子宫腔在着床前沿系膜-对系膜轴形成横向折叠的早期妊娠过程中 3D 子宫折叠模式的动态变化。通过时间序列，我们发现横向折叠是在胚胎间隔形成之前形成的，而植入腔室则在胚胎开始附着时形成。因此，折叠和腔室是两个不同的结构。横向折叠展开形成一个平坦的植入区域，之后胚胎到达其中心进行附着并形成植入后腔室。我们的数据还表明，植入腔室有助于胚胎旋转及其在子宫系膜-对系膜轴上的对齐。使用 WNT5A 和 RBPJ 缺失的小鼠，这些小鼠显示出异常的折叠，我们发现被困在纵向折叠中的胚胎显示出胚胎-子宫轴的不对准、腔室形成异常和植入后形态发生缺陷。这些具有破坏的子宫折叠的小鼠模型为理解对植入和妊娠成功至关重要的基于子宫结构的机制提供了机会。本文有一个相关的“论文背后的人物”采访。
