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Gene that guides egg points to cause of ectopic pregnancy

1 March 2021
Appeared in BioNews 1085

The risk of ectopic pregnancy may be influenced by regulation of a specific gene, according to new research.

Ectopic pregnancies – where the fertilised egg implants and develops outside the uterus – are among the most common prenatal complications, yet the causes are poorly understood. A new study has identified a gene in mice, called Adgrd1, which is active in the fallopian tubes (also known as oviducts) and controls the transit of the eggs from the ovaries to the uterus. 

'Though several risk factors of ectopic pregnancy are known, the precise genetic and molecular mechanisms behind the condition have remained unclear,' said senior author Dr Gavin Wright from the Wellcome Sanger Institute in Cambridge. 'The discovery of the function of Adrgd1 in oviductal fluid regulation, and the consequences of its absence, provides an important clue for researchers studying the causes of ectopic pregnancy in future.'

In the study published in Nature Communications, the team used a large genetic database to show a clear link between Adgrd1 and infertility in mice. They examined ovulation and egg fertilisation and observed that, when Adgrd1 is suppressed, mice retain the embryos within the fallopian tubes and therefore become infertile.

In humans, an egg is released from the ovaries and travels to the uterus via the fallopian tubes. Halfway there, the egg 'pauses' for several days at a specific location known as the 'ampullary-isthmic junction' where, if sperm is present, fertilisation can occur. The journey then continues and, only if fertilised, the egg will implant into the wall of the uterus. 

Several factors regulate the movement of the embryo to the uterus, among them are muscle contractions, cilia (tiny hairs) on the surface of the fallopian tubes which propel the egg towards the uterus, and the flow of the oviductal fluid.

'The flow of oviductal fluid in mammals is somewhat counterintuitive, in that it flows in the opposite direction to the egg's direction of travel,' said first author Dr Enrica Bianchi. 'What we've discovered in this study is that the strength of this flow is normally downregulated by the Adgrd1 gene. But when Adgrd1 is suppressed, the flow is not reduced and the egg cannot seem to move past the ampullary-isthmic junction.'

The team hope to conduct further studies in humans, to explore the role of Adgrd1 and its potential correlation with the incidence of ectopic pregnancy.

Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit
Nature Communications |  23 February 2021
Gene linked to ectopic pregnancy risk
Englemed |  24 February 2021
Gene that helps control egg’s journey sheds light on why ectopic pregnancy may occur
Wellcome Sanger Institute |  23 February 2021
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