Cyclophosphamide suppresses spermatogenesis in the testis of mice through downregulation of miR-34b and miR-34c
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2021
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Abstract
Cyclophosphamide (CP) is commonly used as an anticancer agent but has been associated with high toxicity in several organs, including the testes. In this study, we aimed to evaluate the effects of CP-induced testicular toxicity, using glial cell line-derived neurotrophic factor (GDNF), occludin and transforming growth factor beta 3 (TGF-β3) primary antibodies, and miR-34b and miR-34c expressions. Eighteen young Balb/c male mice were divided into three groups. The control group received no treatment. The mice of CP group were injected 100 mg kg-1 day-1 CP for 5 days, and the same amount of saline was injected in the sham group. The animals were sacrificed 24 hr after the last injection. Immunohistochemical analysis of testicular tissues showed a decrease in both spermatogenic germ cell count and also GDNF, occludin expressions, but an increase in TGF-β3 expression in the CP group compared to the others group. The expressions of miR-34b and miR-34c were examined by qPCR technique, a significant decrease was observed in tissue samples in the CP-treated group. The expression of GDNF, occludin and TGF-β3 plays an important role in testicular injury caused by CP, and the decrease in the expression of miR-34b/c in tissue samples may be an important marker for the detection of testicular damage. © 2021 Wiley-VCH GmbH
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Animals , Cyclophosphamide , Down-Regulation , Male , Mice , MicroRNAs , Spermatogenesis , Testis , complementary DNA , cyclophosphamide , glial cell line derived neurotrophic factor , microRNA , microRNA 16 , microRNA 192 , microRNA 34b , microRNA 34c , neurotrophic factor , occludin , sodium chloride , transforming growth factor beta3 , unclassified drug , cyclophosphamide , microRNA , animal cell , animal experiment , animal model , animal tissue , apoptosis , Article , azoospermia , cell count , cell degeneration , chemotherapy , controlled study , desquamation , DNA synthesis , down regulation , histopathology , immunohistochemistry , immunoreactivity , Leydig cell , male , male fertility , mouse , nonhuman , protein determination , protein expression , protein expression level , protein function , real time polymerase chain reaction , seminiferous tubule , seminiferous tubule epithelium , Sertoli cell , spermatocyte , spermatogenesis , spermatogonium , testis , testis biopsy , testis injury , testis tissue , TUNEL assay , animal , down regulation , genetics , spermatogenesis