Toxaphene is an organochlorine pesticide and environmental contaminant that is concerning due to its atmospheric transport and persistence in soil. In Florida, toxaphene and other organochlorine pesticides were used heavily in agriculture on the north shore of Lake Apopka and they are still detectable in soil. Wild largemouth bass that inhabit the lake and the marshes along the north shore have been exposed to a variety of organochlorine pesticides including dieldrin, methoxychlor, and p,p′-DDE, among others. While these other organochlorine pesticides have been studied for their endocrine disrupting effects in largemouth bass, there is little information for toxaphene. In this study, male and female largemouth bass were given food containing 50 mg/kg toxaphene for almost 3 months, to achieve tissue levels similar to those found in fish at Lake Apopka. Sex-specific toxicity was then evaluated by measuring various reproductive endpoints and transcriptomic changes. In females, gonadosomatic index showed a trend towards reduction (p = 0.051) and plasma vitellogenin was reduced by ~40% relative to controls. However plasma levels of 17β-estradiol and testosterone were not perturbed by toxaphene exposure. These data suggest that toxaphene does not act as a weak estrogen as many other organochlorine pesticides do, but rather appears to be acting as an antiestrogen in female fish. There were no obvious changes in the gonadosomatic index and plasma hormones in male bass. However, ex vivo explant experiments revealed that toxaphene prevented human chorionic gonadotropin-stimulated testosterone production in the testis. This suggested that toxaphene had anti-androgenic effects in males. Subsequent transcriptomic analyses of the testis revealed that androgen receptor/beta-2-microglobulin signaling was up-regulated while insulin-related pathways were suppressed with toxaphene, which could be interpreted as a compensatory response to androgen suppression. In the male liver, the transcriptome analysis revealed an overwhelming suppression in immune-related signaling cascades (e.g. lectin-like receptor and ITSM-Containing Receptor signaling, CD16/CD14 Proinflammatory Monocyte Activation, and CD38/CD3-JUN/FOS/NF-kB Signaling in T-cell Proliferation). Overall, this study showed that toxaphene induced sex-specific effects. The transcriptomic and physiological responses observed can contribute to the development of adverse outcome pathways for toxaphene exposure in fish.

毒杀芬​​是一种有机氯农药和环境污染物，由于其在大气中的迁移和在土壤中的持久性而令人担忧。在佛罗里达州，毒杀芬和其他有机氯杀虫剂在阿波普卡湖北岸的农业中被大量使用，它们仍然可以在土壤中检测到。栖息在北岸湖泊和沼泽地的野生大口黑鲈暴露于多种有机氯杀虫剂，包括狄氏剂、甲氧氯和p,p'-DDE 等。虽然已经研究了这些其他有机氯农药对大口黑鲈的内分泌干扰作用，但关于毒杀芬的信息很少。在这项研究中，雄性和雌性大口黑鲈在近 3 个月的时间里被给予含有 50 毫克/千克毒杀芬的食物，以达到与阿波普卡湖鱼类中发现的相似的组织水平。然后通过测量各种生殖终点和转录组变化来评估性别特异性毒性。在女性中，性腺指数呈下降趋势（p = 0.051) 并且血浆卵黄蛋白原相对于对照减少了约 40%。然而，17β-雌二醇和睾酮的血浆水平不受毒杀芬暴露的影响。这些数据表明毒杀芬不像许多其他有机氯杀虫剂那样充当弱雌激素，而是在雌性鱼类中充当抗雌激素。雄鲈的性腺指数和血浆激素无明显变化。然而，离体外植体实验表明毒杀芬阻止了人绒毛膜促性腺激素刺激的睾丸中睾酮的产生。这表明毒杀芬对男性具有抗雄激素作用。随后对睾丸的转录组学分析表明，雄激素受体/β-2-微球蛋白信号被上调，而胰岛素相关通路被毒杀芬抑制，这可以解释为对雄激素抑制的补偿性反应。在男性肝脏中，转录组分析揭示了免疫相关信号级联反应（例如凝集素样受体和含有 ITSM 的受体信号、CD16/CD14 促炎单核细胞激活和 CD38/CD3-JUN/FOS/NF-kB）的压倒性抑制T细胞增殖中的信号传导）。总的来说，这项研究表明毒杀芬会引起性别特异性影响。观察到的转录组学和生理学反应可能有助于发展鱼类毒杀芬暴露的不良结果途径。CD16/CD14 促炎单核细胞激活，和 T 细胞增殖中的 CD38/CD3-JUN/FOS/NF-kB 信号传导）。总的来说，这项研究表明毒杀芬会引起性别特异性影响。观察到的转录组学和生理学反应可能有助于发展鱼类毒杀芬暴露的不良结果途径。CD16/CD14 促炎单核细胞激活，和 T 细胞增殖中的 CD38/CD3-JUN/FOS/NF-kB 信号传导）。总的来说，这项研究表明毒杀芬会引起性别特异性影响。观察到的转录组学和生理学反应可能有助于发展鱼类毒杀芬暴露的不良结果途径。