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This version published online on October 30, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1654
A more recent version of this article appeared on January 1, 2008
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Submitted on July 24, 2007
Accepted on October 24, 2007

The Expression of activin {beta}A- and {beta}B-subunits, follistatin and activin type II receptors in Fallopian tubes bearing an ectopic pregnancy

Bassem Refaat, Saad Amer, Bolarinde Ola, Neil Chapman, and William Ledger*

Academic Unit of Reproductive and Developmental Medicine, Level 4, The Jessop Wing, Royal Hallamshire Hospital, Sheffield, S10 2SF UK; and University of Nottingham, The Medical School, Derby City General Hospital, Uttoxeter Road, Derby DE22 3NE

* To whom correspondence should be addressed. E-mail: W.Ledger{at}Sheffield.ac.uk.

Ectopic pregnancy is a major cause of maternal morbidity and mortality with increasing incidence worldwide.

Objectives: We have investigated whether epithelia from Fallopian tubes (FTs) bearing an ectopic pregnancy differ from normal tubes in expression of TGF-{beta} family and related proteins and their receptors.

Methodology: Since it is not possible to collect FTs from women carrying a healthy pregnancy, we studied tissue collected at the time of hysterectomy for benign disease. Women were injected with hCG in the days leading up to hysterectomy to produce a state of ‘pseudopregnancy’. Pseudopregnancy status was confirmed by the presence of high serum progesterone levels and the decidualization of the endometrium. 15 Fallopian tubes bearing ectopic pregnancy and 6 pseudopregnant tubes were collected and examined using immunohistochemistry and quantitative RT-PCR.

Results: Immunohistochemistry demonstrated clear staining for the {beta}A-, {beta}B-subunits, ActRIIA, ActRIIB receptors, and follistatin that increased in intensity from the isthmus to the ampulla in both models. However, the intensity of expression of these molecules was stronger in the ectopic pregnancy group when compared to the pseudopregnant group. Quantitative RT-PCR showed Significant decrease in mRNA levels of {beta}A-subunit, activin type IIA and IIB receptors and follistatin in ectopic group (P<0.05) but no changes in {beta}B-subunit (P>0.05). Overall there was an apparent paradox of high concentration of protein but low mRNA expression

Conclusion: Activin-A may stimulate tubal decidualization and trophoblast invasion. A better understanding of the mechanism by which an embryo implants in the tubal epithelium may lead to improved methods for early diagnosis and/or management of ectopic pregnancy.
Key words: Ectopic pregnancy • activin • follistatin • activin receptors • fallopian tube




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