Journal
TOXICOLOGY LETTERS
Volume 219, Issue 1, Pages 65-76Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2013.02.022
Keywords
FGF21; Testicular apoptosis; Type 1 diabetes; Bax/Bcl2; Endoplasmic reticulum stress; Mitochondrial cell death
Categories
Funding
- American Diabetes Association [1-11-BA-17, 1-12-BS-47]
- Starting-Up Fund for Chinese-American Research Institute for Diabetic Complications from Wenzhou Medical College
- National Science Foundation of China [81000294, 81102486, 81170203]
- Fundamental Research Funds for the Central Universities [21611207, 450060323462]
- Development and Reform Commission of Jilin Province [2010019-1]
Ask authors/readers for more resources
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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available