Research Center for Inland Seas (KURCIS), Kobe University, Fukaeminami-machi, Higashinada-ku, Kobe 658-0022, Japan.
Graduate School of Maritime Science, Kobe University, Fukaeminami-machi, Higashinada-ku, Kobe 658-0022, Japan.
Aquat Toxicol. 2023 Jul;260:106553. doi: 10.1016/j.aquatox.2023.106553. Epub 2023 May 6.
Plasticizers are broadly classified as phthalate or nonphthalate. Recently, acetyl tributyl citrate (ATBC), an environmentally friendly nonphthalate plasticizer, was revealed to have the ability to disrupt thyroid hormone activity in fish species. Therefore, we aimed to assess whether ATBC exhibits any sex hormone (i.e., androgenic or estrogenic) activities. First, we examined the effects of ATBC on gonadal sex differentiation. Subsequently, we analyzed the different expression of biomarker genes that respond to endocrine-disrupting chemicals (EDCs) with sexual hormone activity in the liver. We observed normal testes and ovaries after both XX and XY medakas were exposed to ATBC, indicating that ATBC is not an EDCs with strong sex hormone activity and that it does not induce intersex (testis-to-ova or ovo-to-testis) or sex changes in Japanese medaka. The vitellogenin 1 (vtg1) and vitellogenin 2 (vtg2) mRNA expression levels in the liver of XX medakas were significantly reduced compared with those in the control group, whereas the expression levels of these genes in the liver of XY medakas remained unchanged. Finally, we examined the changes in the expression of biomarker genes that respond to EDCs with sex hormone activity in the gonads. The expression levels of biomarker genes did not differ significantly from that of the control group, although the expression levels of gsdf mRNA tended to increase while that of aromatase mRNA tended to decrease in the ovary of XX medakas following ATBC exposure. Conversely, the expression levels of gsdf and aromatase mRNAs in the testis of XY medakas remained unchanged. These results suggest that ATBC does not exhibit estrogenic activity, although it may have weak androgenic activity or no sexual hormone activity.
增塑剂广泛分为邻苯二甲酸酯和非邻苯二甲酸酯。最近，研究发现一种环保型非邻苯二甲酸酯增塑剂——乙酰基三丁基柠檬酸酯（ATBC），具有破坏鱼类甲状腺激素活性的能力。因此，我们旨在评估 ATBC 是否具有任何性激素（即雄激素或雌激素）活性。首先，我们研究了 ATBC 对性腺性别分化的影响。随后，我们分析了不同的生物标志物基因的表达，这些基因对具有性激素活性的内分泌干扰化学物质（EDCs）有反应。我们观察到 XX 和 XY 花鳉暴露于 ATBC 后均表现出正常的睾丸和卵巢，表明 ATBC 不是具有强性激素活性的 EDCs，也不会诱导花鳉的雌雄间性（睾丸-卵巢或卵巢-睾丸）或性别转变。与对照组相比，XX 花鳉肝脏中的卵黄蛋白原 1（vtg1）和卵黄蛋白原 2（vtg2）mRNA 表达水平显著降低，而 XY 花鳉肝脏中的这些基因表达水平保持不变。最后，我们研究了具有性激素活性的 EDCs 反应的生物标志物基因在性腺中的表达变化。尽管 ATBC 暴露后 XX 花鳉卵巢中 gsdf mRNA 的表达水平有增加趋势，而芳香化酶 mRNA 的表达水平有下降趋势，但这些基因的表达水平与对照组相比无显著差异。相反，XY 花鳉睾丸中 gsdf 和芳香化酶 mRNA 的表达水平保持不变。这些结果表明，ATBC 不具有雌激素活性，尽管它可能具有较弱的雄激素活性或没有性激素活性。
