Protective effect of FGF21 on type 1 diabetes-induced testicular apoptotic cell death probably via both mitochondrial- and endoplasmic reticulum stress-dependent pathways in the mouse model |
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Authors: | Xin Jiang Chi Zhang Ying Xin Zhifeng Huang Yi Tan Yadong Huang Yonggang Wang Wenke Feng Xiaokun Li Wei Li Yaqin Qu Lu Cai |
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Institution: | 1. Cancer Center at the First Hospital of Jilin University, Changchun 130021, China;2. KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202, USA;3. The Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical College, Wenzhou 325035, China;4. Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China;5. Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China;6. Department of Urological Surgery, The China-Japan Union hospital of Jilin University, Changchun, 130021, China |
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Abstract: | Fibroblast growth factor 21 (FGF21) is a novel member identified and was reported to express predominantly in pancreas, liver and adipose tissue, and relatively less in other organs, such as the testis. However, the role of FGF21 in the testis has never been addressed. The present study examined FGF21 expression at mRNA level by real-time RT-PCR assay in the testis of fasting and non-fasting mice or mice with type 1 diabetes that was induced with streptozotocin. We also examined the effect of Fgf21 gene deletion or supplementation of the exogenous FGF21 on the testicular apoptotic cell death spontaneously or induced by type 1 diabetes in FGF21 knockout (FGF21-KO) mice. Deletion of Fgf21 gene does not affect testicular cell proliferation, but significantly increases the spontaneous incidence of testicular TUNEL positive cells with increases in the Bax/Bcl2 expression ratio and apoptosis-inducing factor (AIF) expression. Diabetes induced significant increases in testicular TUNEL positive cells, Bax/Bcl2 expression ratio, AIF expression, CHOP and cleaved caspase-12 expression, and oxidative damage, but did not change the expression of cleaved caspase-3 and caspase-8. Deletion of Fgf21 gene also significantly enhances diabetes-induced TUNEL positive cells along with the increased expression of Bax/Bcl2 ratio, AIF, CHOP, cleaved caspase-12, and oxidative damage, which was significantly prevented by the supplementation of exogenous FGF21. These results suggest that Fgf21 gene may involve in maintaining normal spermatogenesis and also protect the germ cells from diabetes-induced apoptotic cell death probably via the prevention of diabetes-induced oxidative damage. |
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Keywords: | FGF21 Testicular apoptosis Type 1 diabetes Bax/Bcl2 Endoplasmic reticulum stress Mitochondrial cell death |
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