Role of activins and inducible nitric oxide in the pathogenesis of ectopic pregnancy in patients with or without Chlamydia trachomatis infection.
Chlamydia trachomatis infection can lead to pelvic inflammatory disease, ectopic pregnancy (EP), infertility, and chronic pelvic pain in women. Activins and inducible nitric oxide synthase (iNOS) are produced by the human fallopian tube, and we speculate that tubal activins and iNOS may be involved in the immune response to C. trachomatis in humans and their pathological alteration may result in tubal pathology and the development of EP. Blood and fallopian tubes were collected from 14 women with EP. Sera were analyzed by enzyme-linked immunosorbent assay to detect antibodies against chlamydial heat shock protein 60 (chsp60) and the major outer membrane protein of C. trachomatis. Confirmation of C. trachomatis serology was made using the microimmunofluorescence test. The patients were classified into three groups according to their serological results, and immunohistochemistry and quantitative reverse transcription-PCR were performed to investigate the expression of candidate molecules by tubal epithelial cells among the three groups. This is the first study to show an increase in the expression of activin betaA subunit, type II receptors, follistatin, and iNOS within the human fallopian tube of EP patients who were serologically positive for C. trachomatis. A similar expression profile was observed in the fallopian tubes with detectable antibodies only against chsp60. These results were shown at the mRNA and protein levels. We suggest that tubal activin A, its type II receptors, follistatin, and NO could be involved in the microbial-mediated immune response within the fallopian tube, and their pathological expression may lead to tubal damage and the development of EP.
Refaat
Bassem
B
Academic Unit of Reproductive and Developmental Medicine, Level 4, The Jessop Wing, Royal Hallamshire Hospital, Sheffield S10 2SF, United Kingdom.
Al-Azemi
Majedah
M
Geary
Ian
I
Eley
Adrian
A
Ledger
William
W
D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D028341:Activins / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001483:Base Sequence; D002690:Chlamydia Infections / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D002692:Chlamydia trachomatis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D005187:Fallopian Tubes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D038681:Follistatin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011271:Pregnancy, Ectopic / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D000907:Antibodies, Bacterial; D017931:DNA Primers; D004269:DNA, Bacterial; C503233:FST protein, human; D038681:Follistatin; D007074:Immunoglobulin G; D012333:RNA, Messenger; C103008:inhibin beta A subunit; D028341:Activins; D028322:Inhibin-beta Subunits; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D030301:Activin Receptors, Type II
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