Rodent blastocysts show remarkably consistent embryonic orientation with respect to the uterine structure, an orientation established at initial implantation which blueprints the direction of future embryo-uterine axis. However, despite this interesting phenomenon having been discovered more than 100 years (since 1894), there have been few molecular mechanisms found responsible for this trait.

In a recent work published in Cell Research, a research group from institute of zoology, Chinese Academy of Sciences, found that in a mouse model with uterine-specific deletion of Rbpj (the nuclear transducer of Notch), the embryo-uterine orientation is disrupted coupled with an abnormal decidual patterning at post-implantation, leading to substantial embryo loss.

This mouse model has further led to the discovery of RBPJ’s critical roles in the uterine compartment: Prior to embryo attachment, Rbpj confers on-time uterine “luminal closure”, a luminal transformation essential for initial embryo-uterine orientation, which is exerted by physically interacting with uterine ERα via Notch pathway-independent mechanisms. While at postimplantation, Rbpj directly regulate uterine matrix metalloproteinase expression through canonical Notch pathway, which is required for normal postimplantation decidual remodeling. These results demonstrated that uterine Rbpj are essential for normal embryo development via instructing the initial embryo-uterine orientation and ensuring normal decidual patterning in a stage-specific manner.

These data provide novel genetic evidence that normal mammalian embryo-uterine orientation requires proper guidance from developmentally controlled uterine signaling.

The paper entitled “Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms” has been online published in Cell Research on 27 June 2014; doi: 10.1038/cr.2014.82. Article link

Illustrative model of uterine Rbpj’s role during the peri-implantation period for embryo development