Toxicant-induced leakage of germ cell-specific proteins from seminiferous tubules in the rat: relationship to blood-testis barrier integrity and prospects for biomonitoring.
Toxicant-induced leakage of germ cell-specific proteins from seminiferous tubules in the rat: relationship to blood-testis barrier integrity and prospects for biomonitoring.
复制标题
DOI：
10.1093/toxsci/kfq210
复制
发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Sharpe RM
中科院分区：
文献类型：
--
作者：
Elkin ND;Piner JA;Sharpe RM
目前，在药物开发过程中对睾丸毒性的评估是基于组织病理学评估。一个灵敏的睾丸毒理学生物标志物可以提供一种活生生的“早期”测量。先前的研究表明，精子发生的中断会导致生殖细胞蛋白从生精小管(STS)泄漏到间质液(IF)，这些蛋白有可能作为生物标志物使用。为了进一步研究这种可能性，成年雄性大鼠被三种被认为具有不同作用部位的睾丸毒物处理：氯化镉影响血-睾丸屏障(BTB)，甲氧基乙酸(MAA)破坏粗线期精母细胞，1，3-二硝基苯(DNB)靶向支持细胞。以考马斯亮蓝为基础的染色凝胶评估蛋白质。免疫组织化学染色鉴定毒物诱导的损伤、血脑屏障的完整性(ZO-1、occludin、N-钙粘蛋白和β-catenin)和功能(生物素)。氯化镉引起蛋白质从STS向IF的剂量依赖性泄漏，与BTB的完整性和功能的丧失一致。其中两种“泄漏”的蛋白质被鉴定为生殖细胞特有的蛋白质，即VASA和脂肪酸结合蛋白9(FABP9)。相反，在MAA诱导或DNB诱导的精子发生中断后，类似的蛋白质泄漏并不明显，这两种处理都不影响BTB的完整性或功能。这些结果表明，生殖细胞特异性蛋白从STS泄漏到IF需要失去BTB的完整性，这意味着使用这种生物标记物对化合物诱导的精子发生中断进行非侵入性监测的潜力非常有限。
Evaluation of testicular toxicity during drug development is currently based on histopathological evaluation. A sensitive biomarker for testicular toxicology could provide an in-life and “early warning” measurement. Previous studies suggested that disruption of spermatogenesis induced leakage of germ cell proteins from seminiferous tubules (STs) into interstitial fluid (IF); such proteins have potential for use as biomarkers. To investigate this possibility further, adult male rats were treated with three testicular toxicants thought to have differing sites of action; cadmium chloride affects the blood-testis barrier (BTB), methoxyacetic acid (MAA) disrupts pachytene spermatocytes, and 1,3-dinitrobenzene (DNB) targets Sertoli cells. IF proteins were assessed by Coomassie-based dye-stained gels. Immunostaining was used to identify toxicant-induced damage (DAZL) and BTB integrity (ZO-1, occludin, N-cadherin, and β-catenin) and function (biotin). Cadmium chloride induced dose-dependent leakage of proteins from STs into IF coincident with loss of integrity and function of the BTB. Two of the “leaked” proteins were identified on Westerns as being germ cell specific, namely VASA and fatty acid–binding protein 9 (FABP9). In contrast, similar protein leakage was not evident after either MAA-induced or DNB-induced disruption of spermatogenesis and neither of these treatments affected BTB integrity or function. These results suggest that loss of BTB integrity is required for germ cell–specific proteins to leak from STs into IF, implying that use of such biomarkers has very limited potential for noninvasive monitoring of compound-induced disruption to spermatogenesis.
登录
查看更多内容
影响因子：
3.2
作者：
FOSTER, PMD;LLOYD, SC;PROUT, MS
通讯作者：
PROUT, MS
DOI：
10.1530/jrf.0.0690125
发表时间：
1983-01-01
期刊：
JOURNAL OF REPRODUCTION AND FERTILITY
影响因子：
--
作者：
SHARPE, RM;COOPER, I
通讯作者：
COOPER, I
影响因子：
3.8
作者：
Siu ER;Mruk DD;Porto CS;Cheng CY
通讯作者：
Cheng CY
影响因子：
3.6
作者：
Korley, R;Pouresmaeili, F;Oko, R
通讯作者：
Oko, R
影响因子：
10.4
作者：
FOSTER, PMD;CREASY, DM;GRAY, TJB
通讯作者：
GRAY, TJB