Tributyltin (TBT) was reported to affect sexual behavior and gametogenesis in fish. However, the modes of action involved are largely unclear. In order to elucidate the toxicological mechanisms of TBT in reproduction, zebrafish (Danio rerio) males were exposed to TBT at concentrations of 100 and 500 ng/L for 28 days. After exposure, the sperm count of the treated fish was sharply decreased though the testis weight and gonadosomatic index remained unchanged. Moreover, reduced number of spermatogonia and spermatozoa and increased spermatocytes were observed in TBT-treated fish by histological observation and PCNA-immunostaining. Increased number of apoptotic-positive spermatocytes was also present in TBT-treated fish, indicating an enhanced apoptosis in these cells. Consistent to decreased number of spermatogonia, down-regulated expressions of genes responsible for germ cell proliferation (cyclind1 and pcna) were observed in TBT-treated fish. In contrast, TBT elevated the expressions of genes involved in meiotic entry and maintenance (aldhla2, sycp3 and dmc1) while suppressed the mRNA level of gene responsible for terminus of meiotic entry (cyp26a1), in agreement with arrested meiosis and reduced sperm count. Furthermore, TBT significantly elevated the ratios of bax/bcl-2 and tnfrsf1a/tnfrsf1b in testis, which are markers for intrinsic- and extrinsic-apoptotic pathways, consistent with the enhanced TUNEL positive signals in spermatocytes. Moreover, TBT also significantly affected the parameter of reproductive behaviors in treated fish (reflected by decreased frequency of meeting, visits and time spent in spawning area). Consistently, the expressions of genes responsible for the modulation of reproductive behaviors in brain (such as cyp19a1b, kiss2, gnrh3 and ompb) were significantly down-regulated in treated-fish. Interestingly, disrupted reproductive behaviors of untreated female fish were also observed in the present study. The present study indicated that TBT might affect the reproduction of zebrafish male by disrupting the spermatogenesis and reproductive behavior of the fish.

中文翻译：

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三丁基锡损害雄性斑马鱼的精子发生和生殖行为。

据报道，三丁基锡（TBT）会影响鱼类的性行为和配子发生。但是，所涉及的行动方式在很大程度上尚不清楚。为了阐明繁殖过程中三丁基锡化合物的毒理机制，将斑马鱼（斑马鱼）雄性以100和500 ng / L的浓度暴露于三丁基锡化合物达28天。暴露后，经治疗的鱼的精子数量急剧下降，尽管睾丸重量和性腺体指数保持不变。此外，通过组织学观察和PCNA免疫染色，在TBT处理的鱼中观察到精原细胞和精子数量减少，精子细胞增加。TBT处理的鱼中还存在凋亡阳性的精母细胞数量增加，表明这些细胞的凋亡增强。与精原细胞数量减少一致，在TBT处理的鱼中观察到了导致生殖细胞增殖的基因（cyclind1和pcna）的表达下调。相反，TBT升高了参与减数分裂进入和维持的基因（aldhla2，sycp3和dmc1）的表达，同时抑制了负责减数分裂进入终点的基因（cyp26a1）的mRNA水平，这与停滞的减数分裂和精子数量减少相一致。此外，TBT显着提高了睾丸中bax / bcl-2和tnfrsf1a / tnfrsf1b的比率，睾丸是内在和外在凋亡途径的标志物，与精母细胞中增强的TUNEL阳性信号一致。此外，TBT还显着影响了经过处理的鱼的生殖行为参数（反映在会面，探视和产卵时间减少上反映出来）。一致地，在处理鱼中，负责调节大脑生殖行为的基因的表达（例如cyp19a1b，kiss2，gnrh3和ompb）显着下调。有趣的是，在本研究中还观察到未经处理的雌鱼的生殖行为受到破坏。本研究表明，TBT可能通过破坏鱼的精子发生和生殖行为而影响斑马鱼雄性的繁殖。