Proteomic analysis of testis biopsies in men treated with transient scrotal hyperthermia reveals the potential targets for contraceptive development |
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Authors: | Hui Zhu Yugui Cui Jin Xie Ling Chen Xiangxiang Chen Xuejiang Guo Yefei Zhu Xinghai Wang Jiansun Tong Zuomin Zhou Yue Jia Yan‐he Lue Amiya Sinha Hikim Christina Wang Ronald S Swerdloff Jiahao Sha |
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Institution: | 1. Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, P. R. China;2. Center of Clinical Reproductive Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, P. R. China;3. Department of Reproductive Medicine, Jiangsu Family Planning Research Institute, Nanjing, P. R. China;4. Division of Endocrinology, Department of Medicine, Harbor‐UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, USA |
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Abstract: | Mild testicular heating safely and reversibly suppresses spermatogenesis. In this study, we attempted to clarify the underlying molecular mechanism(s) involved in heat‐induced spermatogenesis suppression in human testis. We conducted global proteomic analyses of human testicular biopsies before, and at 2 and 9 wk after heat treatment. Thirty‐one and Twenty‐six known proteins were identified with significant differential expression at 2 and 9 wk after heat treatment, respectively. These were used to characterize the cellular and molecular events in the testes when seminiferous epithelia became damaged (2 wk) and recovered (9 wk). At 2 wk post‐treatment, the changed expression of a series of proteins could promote apoptosis or suppress proliferation and cell survival. At 9 wk post‐treatment, the changed expression of proteins mainly promoted cell proliferation, differentiation and survival, but resisted cell apoptosis. Among those heat‐regulated proteins, HNRNPH1 was selected for the further functional study. We found that HNRNPH1 was an anti‐apoptosis protein that could regulate the expression of other heat‐induced proteins. In conclusion, heat‐induced reversible suppression of spermatogenesis occurred by modulating the expression of proteins related to proliferation, differentiation, apoptosis and cell survival pathways. These differentially expressed proteins were found to be key molecular targets affecting spermatogenesis after heat treatment. |
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Keywords: | Animal proteomics Apoptosis HNRNPH1 protein Human testis Transient scrotal hyperthermia |
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