CONACYT, Mexico; Departamento de Recursos del Mar, Cinvestav Unidad Mérida, Mérida, Yucatán 97310, Mexico.
Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.
Aquat Toxicol. 2018 Aug;201:162-173. doi: 10.1016/j.aquatox.2018.06.005. Epub 2018 Jun 8.
Despite a wide number of toxicological studies that describe benzo[a]pyrene (BaP) effects, the metabolic mechanisms that underlie these effects in fish are largely unknown. Of great concern is the presence of BaP in aquatic systems, especially those in close proximity to human activity leading to consumption of potentially contaminated foods. BaP is a known carcinogen and it has been reported to have adverse effects on the survival, development and reproduction of fish. The purpose of this study was to investigate if a low dose of BaP can alter genes and key metabolic pathways in the liver and testis in male adult tilapia, and whether these could be associated with biological endpoints disruption. We used both high-throughput RNA-Sequencing to assess whole genome gene expression following repeated intraperitoneal injections of 3 mg/kg of BaP (every 6 days for 26 days) and morphometric endpoints as indicators of general health. Condition factor (K) along with hepatosomatic and gonadosomatic indices (morphometric parameters) were significantly lower in BaP-treated fish than in controls. BaP exposure induced important changes in the gene expression pattern in liver and testis as revealed by both Pathway and Gene Ontology (GO) analyses. Alterations that were shared by both tissues included arachidonic acid metabolism, androgen receptor to prostate-specific antigen signaling, and insulin-associated effects on lipogenesis. The most salient liver-specific effects included: biological processes involved in detoxification, IL6-associated insulin resistance, mTOR hyperactivation, mitotic cytokinesis, spindle pole and microtubule binding. BaP effects that were confined to the testis included: immune system functions, inflammatory response, estrogen and androgen metabolic pathways. Taken together, gene expression and morphometric end point data indicate that the reproductive success of adult male tilapia could be compromised as a result of BaP exposure. These results constitute new insights on the mechanism of action of low dose BaP in a non-model organism (tilapia).
尽管有大量毒理学研究描述了苯并[a]芘（BaP）的影响，但鱼类中这些影响的代谢机制在很大程度上尚不清楚。人们非常关注的是 BaP 在水生系统中的存在，特别是在靠近人类活动的地方，这些地方可能导致食用受污染的食物。BaP 是一种已知的致癌物质，据报道它对鱼类的生存、发育和繁殖有不良影响。本研究的目的是研究低剂量 BaP 是否会改变雄性成年罗非鱼肝脏和睾丸中的基因和关键代谢途径，以及这些基因和途径是否与生物终点的破坏有关。我们使用高通量 RNA 测序来评估重复腹腔注射 3mg/kg BaP（每 6 天一次，共 26 天）后基因的全基因组表达，以及形态计量终点作为一般健康的指标。与对照组相比，BaP 处理组的条件因子（K）以及肝体比和性腺体比（形态计量参数）显著降低。BaP 暴露诱导了肝脏和睾丸中基因表达模式的重要变化，这一点通过通路和基因本体（GO）分析得到了揭示。两种组织都存在的变化包括花生四烯酸代谢、雄激素受体向前列腺特异性抗原信号转导以及胰岛素对脂肪生成的影响。最显著的肝脏特异性效应包括：与解毒相关的生物过程、IL6 相关的胰岛素抵抗、mTOR 过度激活、有丝分裂细胞分裂、纺锤体极和微管结合。仅局限于睾丸的 BaP 效应包括：免疫系统功能、炎症反应、雌激素和雄激素代谢途径。总之，基因表达和形态计量终点数据表明，雄性成年罗非鱼的生殖成功率可能会因 BaP 暴露而受到损害。这些结果为低剂量 BaP 在非模式生物（罗非鱼）中的作用机制提供了新的见解。
