Studies on the characteristics and mechanisms of testicular toxicity induced by Hydroxyurea

Autor:	Chun-qi Wu, Yongwei Luo, Ming-yang Liao, Zuyue Sun, Li Zhou
Rok vydání:	2015
Předmět:	Male Fas Ligand Protein Health Toxicology and Mutagenesis Blotting Western Apoptosis Mice Transgenic Periodic acid–Schiff stain Toxicology Fas ligand Western blot Testis In Situ Nick-End Labeling medicine Animals Hydroxyurea fas Receptor Caspase TUNEL assay biology medicine.diagnostic_test Molecular biology Up-Regulation Mice Inbred C57BL medicine.anatomical_structure Mice Inbred DBA Caspases biology.protein Spermatogenesis Injections Intraperitoneal Germ cell
Zdroj:	Toxicology Mechanisms and Methods. 25:396-401
ISSN:	1537-6524 1537-6516
DOI:	10.3109/15376516.2015.1045657
Popis:	Apoptosis plays a dominant role in both spontaneous spermatogenesis and germ cell death. This study was aimed to investigate the functions of related genes in testicular germ cell death induced by Hydroxyurea (HU).Wild-type (WT) and FasL transgenic (TG) DBA/C57BL mice were intraperitoneal injected with 400 mg/kg HU. Twelve hours later, testes were collected. Histomorphology of testis was observed by staining with Periodic Acid Schiff (PAS). Apoptosis was assessed by TUNEL assay. mRNA and protein levels of related genes were evaluated by quantitative RT-PCR and Western blot, respectively.The 2 × 2 factorial design comparative experiments between the WT and TG mice showed that the TG mice exhibited a higher basal apoptotic index. The basal mRNA levels of Fas and FasL and protein levels of Fas, FasL, Caspase-3, Caspase-8 and Caspase-9 in the TG mice were also higher than that in the WT mice. Twelve hours after injection of HU, the testicular tubules exhibited no significantly morphological changes but apoptosis index remarkably increased in both the WT and TG mice, with the latter having the higher amplitude. Although, HU up-regulated the mRNA of apoptosis-related genes, such as Fas and FasL, in both the TG and WT mice, the increased amplitude was more obvious in the TG mice. By Western blot analysis, apoptosis-related proteins Fas, FasL Caspase-3, Caspase-8 and Caspase-9 were significantly increased in both the WT and TG mice, with the TG mice exhibiting a greater up-regulation.Germ cell apoptosis induced by the HU treatment may be related to the FasL-mediated signal transduction pathway.
Databáze:	OpenAIRE
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