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.

Design

Experimental animal study.

Setting

University laboratory animal service center.

Animal(s)

Adult female mice with regular estrous cycles.

Intervention(s)

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

Main Outcome Measure(s)

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-α 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.

Result(s)

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-α 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.

Conclusion(s)

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.

Key Words: Chlamydia trachomatis, cystic fibrosis transmembrane conductance regulator, TNF-α, implantation