Abnormally up-regulated cystic fibrosis transmembrane conductance regulator expression and uterine fluid accumulation contribute to Chlamydia trachomatis-induced female infertility.
OBJECTIVE
To investigate whether abnormal expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic adenosine 3':5' monophosphate (cAMP)-activated chloride channel, and uterine fluid accumulation upon Chlamydia trachomatis infection may result in implantation failure, thus contributing to C. trachomatis-induced female infertility.


METHODS
Experimental animal study.


METHODS
University laboratory animal service center.


METHODS
Adult female mice with regular estrous cycles.


METHODS
Intrauterine injection of C. trachomatis lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and estrogen (E) at diestrus and preimplantation.


METHODS
The CFTR messenger RNA (mRNA) and protein levels were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively, in mouse uterus treated with C. trachomatis LPS, TNF-alpha or E. Endometrial electrolyte transport and uterine fluid accumulation were determined by the short circuit current and uterine wet weight, respectively. Number of implanted embryos was also counted to demonstrate the effect of treatments.


RESULTS
Uterine C. trachomatis LPS infection induced up-regulation of CFTR expression with enhanced anion secretion, abnormal fluid accumulation in mouse uterus at diestrus, and reduced implantation rate. Administration of exogenous TNF-alpha to mouse uterus mimicked the C. trachomatis LPS infection-induced CFTR up-regulation, enhanced CFTR channel activity, and fluid accumulation. Abnormal uterine fluid accumulation and implantation failure were also observed when CFTR was up-regulated by E.


CONCLUSIONS
The present results suggest that C. trachomatis infection-induced release of cytokines could abnormally up-regulate CFTR expression leading to abnormal uterine fluid accumulation, which may result in infertility often associated with C. trachomatis infection.
He
Qiong
Q
Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, People's Republic of China.
Tsang
Lai Ling
LL
Ajonuma
Louis Chukwuemeka
LC
Chan
Hsiao Chang
HC
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002690:Chlamydia Infections / Q000150:complications* / Q000235:genetics; D002692:Chlamydia trachomatis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D010064:Embryo Implantation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D007247:Infertility, Female / Q000209:etiology* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D014599:Uterus / Q000502:physiology
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004958:Estradiol