Dataset Information

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.

SUBMITTER: Yan C

PROVIDER: S-EPMC4970767 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis.

Yan Chen C Lang Qin Q Huijuan Liao L Jiang Xie X Ming Yang Y Huaqin Sun S Wenming Xu X

PloS one 20160802 8

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 ...[more]

PMID: 27483469

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Project description:Spermatogenesis in mammals is a cyclic process of spermatogenic cell development in the seminiferous epithelium that can be subdivided into 12 subsequent stages. Histological staging analysis of testis sections, specifically of seminiferous tubule cross-sections, is the only effective method to evaluate the quality of the spermatogenic process and to determine developmental defects leading to infertility. Such staging analysis, however, is tedious and time-consuming, and it may take a long time to become proficient. We now have developed a Computerized Staging system of Spermatogenesis (CSS) for mouse testis sections through learning of an expert with decades of experience in mouse testis staging. The development of the CSS system comprised three major parts: 1) Developing computational image analysis models for mouse testis sections; 2) Automated classification of each seminiferous tubule cross-section into three stage groups: Early Stages (ES: stages I-V), Middle Stages (MS: stages VI-VIII), and Late Stages (LS: stages IV-XII); 3) Automated classification of MS into distinct stages VI, VII-mVIII, and late VIII based on newly developed histomorphological features. A cohort of 40 H&E stained normal mouse testis sections was built according to three modules where 28 cross-sections were leveraged for developing tubule region segmentation, spermatogenic cells types and multi-concentric-layers segmentation models. The rest of 12 testis cross-sections, approximately 2314 tubules whose stages were manually annotated by two expert testis histologists, served as the basis for developing the CSS system. The CSS system's accuracy of mean and standard deviation (MSD) in identifying ES, MS, and LS were 0.93 ± 0.03, 0.94 ± 0.11, and 0.89 ± 0.05 and 0.85 ± 0.12, 0.88 ± 0.07, and 0.96 ± 0.04 for one with 5 years of experience, respectively. The CSS system's accuracy of MSD in identifying stages VI, VII-mVIII, and late VIII are 0.74 ± 0.03, 0.85 ± 0.04, and 0.78 ± 0.06 and 0.34 ± 0.18, 0.78 ± 0.16, and 0.44 ± 0.25 for one with 5 years of experience, respectively. In terms of time it takes to collect these data, it takes on average 3 hours for a histologist and 1.87 hours for the CSS system to finish evaluating an entire testis section (computed with a PC (I7-6800k 4.0 GHzwith 32GB of RAM & 256G SSD) and a Titan 1080Ti GPU). Therefore, the CSS system is more accurate and faster compared to a human histologist in staging, and further optimization and development will not only lead to a complete staging of all 12 stages of mouse spermatogenesis but also could aid in the future diagnosis of human infertility. Moreover, the top-ranking histomorphological features identified by the CSS classifier are consistent with the primary features used by histologists in discriminating stages VI, VII-mVIII, and late VIII.

Dataset Information

CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis.

Publications

CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis.

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