Smoking link to ectopic pregnancy

 
BBC News   - 27 September 2010
 
 
Smoking is thought to increase the risk of an ectopic pregnancy by up to four times A chemical in cigarette smoke has been found to cause a reaction which can lead to ectopic pregnancies, according to Edinburgh scientists.

Research from experts at Edinburgh University said Cotinine triggered a reaction which increased a protein in the Fallopian tubes.

They said the protein, called PROKR1, raised the risk of an egg implanting outside the womb.

Details of the study were published in the American Journal of Pathology.

PROKR1 allows pregnancies to implant correctly inside the womb, but its presence in the Fallopian tubes is believed to increase the risks of this happening outside the womb.

The study found that women who smoked and developed an ectopic pregnancy had twice as much PROKR1 in their Fallopian tubes as women who did not smoke and had previously had a healthy pregnancy.

"This shows that components of cigarette smoke also enter the blood stream and affect seemingly unconnected parts of the body"

End Quote Dr Andrew Horne Edinburgh University
Researchers believe that too much of the protein prevents the muscles in the walls of the Fallopian tubes from contracting, which in turn hinders the transfer of the egg to the womb.

Dr Andrew Horne, of the university's centre for reproductive biology, said: "This research provides scientific evidence so that we can understand why women who smoke are more at risk of ectopic pregnancies and how smoking impacts on reproductive health.

"While it may be easy to understand why inhalation of smoke affects the lungs, this shows that components of cigarette smoke also enter the blood stream and affect seemingly unconnected parts of the body like the reproductive tract."

The study, funded by Wellbeing of Women, analysed tissue samples from female smokers and non-smokers, and from women who had previously had ectopic and healthy pregnancies.

Smoking is thought to increase the risk of an ectopic pregnancy by up to four times.

There are more than 30,000 ectopic pregnancies in the UK each year, with the egg implanting in the Fallopian tube in 98% of cases.

This can cause the tube to rupture and lead to internal bleeding and fertility problems in the future.

Around one in 50 pregnancies in the western world is ectopic. The condition is the leading cause of maternal mortality in the first three months of pregnancy.

http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-11418432 



Cotinine Exposure Increases Fallopian Tube PROKR1 Expression via Nicotinic AChR alpha-7. A Potential Mechanism Explaining the Link between Smoking and Tubal Ectopic Pregnancy
 
American Journal of Pathology
Published online before print September 23, 2010
 
Julie L.V. Shaw, Elizabeth Oliver, Kai-Fai Lee, Gary Entrican, Henry N. Jabbour, Hilary O.D. Critchley, and Andrew W. Horne
 
Abstract
 
Tubal ectopic pregnancy (EP) is the most common cause of maternal mortality in the first trimester of pregnancy; however, its etiology is uncertain. In EP, embryo retention within the Fallopian tube (FT) is thought to be due to impaired smooth muscle contractility (SMC) and alterations in the tubal microenvironment. Smoking is a major risk factor for EP. FTs from women with EP exhibit altered prokineticin receptor-1 (PROKR1) expression, the receptor for prokineticins (PROK). PROK1 is angiogenic, regulates SMC, and is involved in intrauterine implantation.

We hypothesized that smoking predisposes women to EP by altering tubal PROKR1 expression. Sera/FT were collected at hysterectomy (n = 21). Serum levels of the smoking metabolite, cotinine, were measured by enzyme-linked immunosorbent assay. FTs were analyzed by q-RT-PCR, immunohistochemistry, and Western blotting for expression of PROKR1 and the predicted cotinine receptor, nicotinic acetylcholine receptor alpha-7 (AChR alpha-7). FT explants (n = 4) and oviductal epithelial cells (cell line OE-E6/E7) were treated with cotinine and an nAChR alpha-7 antagonist.

PROKR1 transcription was higher in FTs from smokers (P < 0.01). nAChR alpha-7 expression was demonstrated in FT epithelium. Cotinine treatment of FT explants and OE-E6/E7 cells increased PROKR1 expression (P < 0.05), which was negated by cotreatment with nAChR alpha-7 antagonist.

Smoking targets human FTs via nAChR alpha-7 to increase tubal PROKR1, leading to alterations in the tubal microenvironment that could predispose to EP.
 
http://ajp.amjpathol.org/cgi/content/abstract/ajpath.2010.100243v1