Reproduction Abstracts

ADGRD1 is a member of the adhesion G protein-coupled receptors (aGPCRs), a family of membrane proteins that are categorised by the presence of a GAIN (GPCR autoproteolysis-inducing) domain between a large N-terminal extracellular region that is thought to bind signal-initiating ligands, and the signal-transducing G-protein-coupled seven transmembrane helices. The role and function of many aGPRCs is unclear and most of them are ‘orphan’ receptors, having no identified ligand. A mouse line specifically lacking Adgrd1 has been generated at the Sanger Institute and homozygous females were found to be infertile: no pregnancies were detected, and no pups were delivered. To understand the molecular basis ofAdgrd1 function in female fertility, we are trying to determine exactly when and where ADGRD1 is expressed and to identify its ligand. Normal-looking eggs are ovulated in response to hormonal stimulation and the number of zygotes recovered after mating is similar in WT and in Adgrd1^−/− females. Furthermore, the lack of embryo implantation sites and their absence from the uterus point to an impairment of transport along the oviduct. Ciliary beating and muscle contractions propel embryos towards the uterus, and it is unclear if and how ADGRD1 is involved in any of these processes. If embryos are retained in the oviduct this might lead to ectopic pregnancies. It is estimated that in the UK around one in ninety pregnancies develops into an ectopic one therefore, studying the role of genes like Adgrd1, can help to understand the causes of ectopic pregnancy, and may result in the development of a diagnostic test.