Involvement of cystic fibrosis transmembrane conductance regulator (CFTR) in the pathogenesis of hydrosalpinx induced by Chlamydia trachomatis infection.
BACKGROUND
Genital Chlamydia (C) trachomatis infection has been recognized as the single most common cause of pelvic inflammatory disease leading to severe tubal damage, ectopic pregnancy, infertility and hydrosalpinx. However, the mechanism underlying the formation of hydrosalpinx induced by C. trachomatis infection remains largely unknown. We performed this study to determine the involvement of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel that regulates epithelial electrolyte and fluid secretion, in hydrosalpinx fluid formation.


METHODS
Western blot analysis was used to determine CFTR expression in the hydrosalpinges that were seen on the ultrasound scans of infertile assisted reproduction treatment patients. Correlation with C. trachomatis infection was done by testing patients' sera for C. trachomatis immunoglobulin G antibody titer using a Capita enzyme-linked immunosorbent assay based kit. CFTR involvement was further verified in a rat C. trachomatis infection model and confirmed using CFTR mutant (CFTR(tm1Unc)) mice.


RESULTS
Here we report on the up-regulated expression of CFTR in the hydrosalpinx tissues of infertile patients with detectable serum levels of C. trachomatis antibody (immunoglobulin G). In a rat model, increased CFTR expression and fluid accumulation could be observed in the uterine horns infected with C. trachomatis elementary bodies, which was reversed by antibiotics treatment. In C. trachomatis-infected CFTR(tm1Unc) mice, however, no detectable fluid accumulation was observed.


CONCLUSIONS
These findings suggest the involvement of CFTR in the pathogenesis of hydrosalpinx fluid formation and may provide grounds for a better treatment strategy to improve assisted reproduction treatment outcome in infertile patients with hydrosalpinx.
Ajonuma
Louis Chukwuemeka
LC
Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Chan
Paul Kay Sheung
PK
Ng
Ernest Hung Yu
EH
Fok
Kin Lam
KL
Wong
Connie Hau Yan
CH
Tsang
Lai Ling
LL
Tang
Xiao Xiao
XX
Ho
Lok Sze
LS
Lau
Miu Ching
MC
Chung
Chin Man
CM
He
Qiong
Q
Huang
Hong Yi
HY
Yang
Dong Zi
DZ
Rowlands
Dewi Kenneth
DK
Chung
Yiu Wa
YW
Chan
Hsiao Chang
HC
D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000302:isolation & purification*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004195:Disease Models, Animal; D005184:Fallopian Tube Diseases / Q000378:metabolism* / Q000382:microbiology*; D005260:Female; D006801:Humans; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley
D000907:Antibodies, Bacterial; D019005:Cystic Fibrosis Transmembrane Conductance Regulator