title: CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis.
abstract: Cystic fibrosis is the most common genetic disease among Caucasians and affects tissues including lung, pancreas and reproductive tracts. It has been shown that Endoplasmic Reticulum (ER) stress and heat shock response are two major deregulated functional modules related to CFTR dysfunction. To identify the impact of CFTR deletion during spermatogenesis, we examined the expression of spermiogenesis-related genes in the testis of CFTR mutant mice (CF mice). We confirmed expression changes of MSY2, a germ cell specific RNA binding protein, resulting from deletion of CFTR in testis. Furthermore, real time PCR and Western blot results showed that an inflammatory response was activated in CF mice testis, as reflected by the altered expression of cytokines. We demonstrate for the first time that expression of MSY2 is decreased in CF mice. Our results suggest that CFTR deletion in testis influences inflammatory responses and these features are likely to be due to the unique environment of the seminiferous tubule during the spermatogenesis process. The current study also suggests avenues to understand the pathophysiology of CFTR during spermatogenesis and provides targets for the possible treatment of CFTR-related infertility.
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|Key Laboratory of Birth Defects and Related disease of Women and Children, Ministry of Education (Sichuan University), West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|SCU-CUHK Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lang
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|Key Laboratory of Birth Defects and Related disease of Women and Children, Ministry of Education (Sichuan University), West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|SCU-CUHK Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Liao
authors.initials: L
authors.lastname: Huijuan
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|Third People's Hospital of Chengdu, the Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu 610031, Sichuan, China.
authors.forename: Xie
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|Key Laboratory of Birth Defects and Related disease of Women and Children, Ministry of Education (Sichuan University), West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|SCU-CUHK Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ming
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|Key Laboratory of Birth Defects and Related disease of Women and Children, Ministry of Education (Sichuan University), West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|SCU-CUHK Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Huaqin
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|Key Laboratory of Birth Defects and Related disease of Women and Children, Ministry of Education (Sichuan University), West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.|SCU-CUHK Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wenming
mesh_terms: D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000276:immunology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D008297:Male; D018181:Mice, Inbred CFTR; D016328:NF-kappa B / Q000276:immunology; D016601:RNA-Binding Proteins / Q000235:genetics; D015398:Signal Transduction; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D050995:Voltage-Dependent Anion Channel 1 / Q000276:immunology*
chemical_list: D016328:NF-kappa B; D016601:RNA-Binding Proteins; C494763:Vdac1 protein, mouse; C116047:Ybx2 protein, mouse; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D050995:Voltage-Dependent Anion Channel 1