The expression of activin-betaA- and -betaB-subunits, follistatin, and activin type II receptors in fallopian tubes bearing an ectopic pregnancy.
BACKGROUND
Ectopic pregnancy is a major cause of maternal morbidity and mortality with increasing incidence worldwide.


OBJECTIVE
We 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.


METHODS
Because 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 human chorionic gonadotropin 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. Fifteen FTs bearing ectopic pregnancy and six pseudopregnant tubes were collected and examined using immunohistochemistry and quantitative RT-PCR.


RESULTS
Immunohistochemistry demonstrated clear staining for the betaA- and betaB-subunits, type II receptor group comprising the activin type IIA and type IIB receptors, and follistatin, which 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 with the pseudopregnant group. Quantitative RT-PCR showed significant decrease in mRNA levels of betaA-subunit, activin type IIA and IIB receptors, and follistatin in ectopic group (P < 0.05) but no changes in betaB-subunit (P > 0.05). Overall, there was an apparent paradox of high concentration of protein but low mRNA expression.


CONCLUSIONS
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.
Refaat
Bassem
B
Academic Unit of Reproductive and Developmental Medicine, Level 4, The Jessop Wing, Royal Hallamshire Hospital, Sheffield S10 2SF, United Kingdom.
Amer
Saad
S
Ola
Bolarinde
B
Chapman
Neil
N
Ledger
William
W
D030301:Activin Receptors, Type II / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D005187:Fallopian Tubes / Q000378:metabolism*; D005260:Female; D038681:Follistatin / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D028322:Inhibin-beta Subunits / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000378:metabolism*; D011555:Pseudopregnancy / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D038681:Follistatin; C422402:INHBB protein, human; D012333:RNA, Messenger; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits; D030301:Activin Receptors, Type II