Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States of America; UF Genetics Institute, University of Florida, Gainesville, FL, United States of America.
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States of America; Southern California Coastal Water Research Project Authority, Costa Mesa, CA 92626, United States of America.
Comp Biochem Physiol Part D Genomics Proteomics. 2020 Dec;36:100746. doi: 10.1016/j.cbd.2020.100746. Epub 2020 Sep 19.
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，由于其在大气中的传输和在土壤中的持久性而受到关注。在佛罗里达州，毒杀芬和其他有机氯农药在阿波卡湖北岸的农业中大量使用，它们仍然可以在土壤中检测到。栖息在该湖和北岸湿地的大嘴黑鲈已经接触到了各种有机氯农药，包括狄氏剂、甲氧氯和 p,p'-DDE 等。虽然这些其他有机氯农药的内分泌干扰作用已经在大嘴黑鲈中进行了研究，但关于毒杀芬的信息却很少。在这项研究中，雄性和雌性大嘴黑鲈连续近 3 个月食用含有 50mg/kg 毒杀芬的食物，以达到与在阿波卡湖发现的鱼类相似的组织水平。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。在雌性中，性腺体指数显示出降低的趋势（p=0.051），并且相对于对照组，血浆卵黄蛋白原降低了约 40%。然而，毒杀芬暴露并没有干扰血浆 17β-雌二醇和睾酮的水平。这些数据表明，毒杀芬不像许多其他有机氯农药那样作为弱雌激素起作用，而是在雌性鱼类中似乎作为一种抗雌激素。雄性鲈鱼的性腺体指数和血浆激素没有明显变化。然而，离体组织培养实验表明，毒杀芬阻止了人绒毛膜促性腺激素刺激睾丸中睾酮的产生。这表明毒杀芬对雄性具有抗雄激素作用。随后对睾丸的转录组分析显示，雄激素受体/β-2-微球蛋白信号通路被上调，而胰岛素相关途径被抑制，这可以解释为对雄激素抑制的代偿反应。在雄性肝脏中，转录组分析显示免疫相关信号级联（例如凝集素样受体和 ITSM 包含受体信号、CD16/CD14 促炎单核细胞激活和 CD38/CD3-JUN/FOS/NF-κB 信号在 T 细胞增殖中）被压倒性地抑制。总的来说，这项研究表明毒杀芬引起了性别特异性效应。观察到的转录组和生理反应可以为鱼类接触毒杀芬的不良结局途径的发展做出贡献。
