Qiong He1, Lai Ling Tsang, Louis Chukwuemeka Ajonuma, Hsiao Chang Chan. 1. 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.
Abstract
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-alpha (TNF-alpha), 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-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. 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-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. 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. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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), tumornecrosis factor-alpha (TNF-alpha), 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-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. 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-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. 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. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Authors: Ana Teles; Anne Schumacher; Marie-Cristine Kühnle; Nadja Linzke; Catharina Thuere; Peter Reichardt; Carlos Eduardo Tadokoro; Günter J Hämmerling; Ana Claudia Zenclussen Journal: Front Immunol Date: 2013-06-20 Impact factor: 7.561