Skip to Content
Merck
  • Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit.

Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit.

Nature communications (2021-02-25)
Enrica Bianchi, Yi Sun, Alexandra Almansa-Ordonez, Michael Woods, David Goulding, Nadia Martinez-Martin, Gavin J Wright
ABSTRACT

Dysfunction of embryo transport causes ectopic pregnancy which affects approximately 2% of conceptions in the US and Europe, and is the most common cause of pregnancy-related death in the first trimester. Embryo transit involves a valve-like tubal-locking phenomenon that temporarily arrests oocytes at the ampullary-isthmic junction (AIJ) where fertilisation occurs, but the mechanisms involved are unknown. Here we show that female mice lacking the orphan adhesion G-protein coupled receptor Adgrd1 are sterile because they do not relieve the AIJ restraining mechanism, inappropriately retaining embryos within the oviduct. Adgrd1 is expressed on the oviductal epithelium and the post-ovulatory attenuation of tubal fluid flow is dysregulated in Adgrd1-deficient mice. Using a large-scale extracellular protein interaction screen, we identified Plxdc2 as an activating ligand for Adgrd1 displayed on cumulus cells. Our findings demonstrate that regulating oviductal fluid flow by Adgrd1 controls embryo transit and we present a model where embryo arrest at the AIJ is due to the balance of abovarial ciliary action and the force of adovarial tubal fluid flow, and in wild-type oviducts, fluid flow is gradually attenuated through Adgrd1 activation to enable embryo release. Our findings provide important insights into the molecular mechanisms involved in embryo transport in mice.

MATERIALS
Product Number
Brand
Product Description

Supelco
Micro particles based on polystyrene, analytical standard, size: 15 μm
Sigma-Aldrich
Monoclonal Anti-Actin, α-Smooth Muscle, clone 1A4, ascites fluid
Sigma-Aldrich
Glass beads, acid-washed, ≤106 μm (−140 U.S. sieve)
Sigma-Aldrich
Adenosine 3′,5′-cyclic monophosphate tris salt, ≥97% (HPLC), powder