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Article ; Online: Aberrant uterine folding in mice disrupts implantation chamber formation and alignment of embryo-uterine axes.

Madhavan, Manoj K / DeMayo, Francesco J / Lydon, John P / Joshi, Niraj R / Fazleabas, Asgerally T / Arora, Ripla

Development (Cambridge, England)

2022  Volume 149, Issue 11

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 ...

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.
MeSH term(s) Animals ; Embryo Implantation ; Embryo, Mammalian ; Epithelium ; Female ; Horses ; Humans ; Mammals ; Mice ; Pregnancy ; Uterus
Language English
Publishing date 2022-06-13
Publishing country England
Document type Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID 90607-4
ISSN 1477-9129 ; 0950-1991
ISSN (online) 1477-9129
ISSN 0950-1991
DOI 10.1242/dev.200300
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