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Environmentally relevant mixture of S-metolachlor and its two metabolites affects thyroid metabolism in zebrafish embryos.
Aquatic Toxicology ( IF 4.5 ) Pub Date : 2020-02-07 , DOI: 10.1016/j.aquatox.2020.105444 Eliška Rozmánková 1 , Marek Pípal 2 , Lucie Bláhová 2 , Naveen Njattuvetty Chandran 2 , Bénédicte Morin 3 , Patrice Gonzalez 3 , Luděk Bláha 2
Aquatic Toxicology ( IF 4.5 ) Pub Date : 2020-02-07 , DOI: 10.1016/j.aquatox.2020.105444 Eliška Rozmánková 1 , Marek Pípal 2 , Lucie Bláhová 2 , Naveen Njattuvetty Chandran 2 , Bénédicte Morin 3 , Patrice Gonzalez 3 , Luděk Bláha 2
Affiliation
Herbicides and their metabolites are often detected in water bodies where they may cause adverse effects to non-target organisms. Their effects at environmentally relevant concentrations are often unclear, especially concerning mixtures of pesticides. This study thus investigated the impacts of one of the most used herbicides: S-metolachlor and its two metabolites, metolachlor oxanilic acid (MOA) and metolachlor ethanesulfonic acid (MESA) on the development of zebrafish embryos (Danio rerio). Embryos were exposed to the individual substances and their environmentally relevant mixture until 120 hpf (hours post-fertilization). The focus was set on sublethal endpoints such as malformations, hatching success, length of fish larvae, spontaneous movements, heart rate and locomotion. Moreover, expression levels of eight genes linked to the thyroid system disruption, oxidative stress defense, mitochondrial metabolism, regulation of cell cycle and retinoic acid (RA) signaling pathway were analyzed. Exposure to S-metolachlor (1 μg/L) and the pesticide mixture (1 μg/L of each substance) significantly reduced spontaneous tail movements of 21 hpf embryos. Few rare developmental malformations were observed, but only in larvae exposed to more than 100 μg/L of individual substances (craniofacial deformation, non-inflated gas bladder, yolk sac malabsorption) and to 30 μg/L of each substance in the pesticide mixture (spine deformation). No effect on hatching success, length of larvae, heart rate or larvae locomotion were found. Strong responses were detected at the molecular level including induction of p53 gene regulating the cell cycle (the pesticide mixture - 1 μg/L of each substance; MESA 30 μg/L; and MOA 100 μg/L), as induction of cyp26a1 gene encoding cytochrome P450 (pesticide mixture - 1 μg/L of each substance). Genes implicated in the thyroid system regulation (dio2, thra, thrb) were all overexpressed by the environmentally relevant concentrations of the pesticide mixture (1 μg/L of each substance) and MESA metabolite (1 μg/L). Zebrafish thyroid system disruption was revealed by the overexpressed genes, as well as by some related developmental malformations (mainly gas bladder and yolk sac abnormalities), and reduced spontaneous tail movements. Thus, the thyroid system disruption represents a likely hypothesis behind the effects caused by the low environmental concentrations of S-metolachlor, its two metabolites and their mixture.
中文翻译:
与环境相关的S-甲草胺及其两种代谢物的混合物会影响斑马鱼胚胎中的甲状腺代谢。
除草剂及其代谢物经常在水体中被检测到,它们可能对非目标生物造成不利影响。它们在环境相关浓度下的作用通常不清楚,特别是在农药混合物方面。因此,这项研究调查了一种最常用的除草剂:S-异丙甲草胺及其两种代谢产物,甲草胺草酸苯甲酸(MOA)和甲草胺乙磺酸(MESA)对斑马鱼胚胎(Danio rerio)发育的影响。胚胎暴露于单个物质及其与环境相关的混合物,直到120 hpf(受精后数小时)。重点放在致死性终点,例如畸形,孵化成功,幼虫长度,自发运动,心率和运动。此外,分析了与甲状腺系统破坏,氧化应激防御,线粒体代谢,细胞周期调节和视黄酸(RA)信号通路相关的八个基因的表达水平。暴露于异丙甲草胺(1μg/ L)和农药混合物(每种物质1μg/ L)会显着降低21 hpf胚胎的自发尾巴运动。很少观察到罕见的发育畸形,但是仅在暴露于100μg/ L以上的单个物质(颅面变形,未充气的气囊,卵黄囊吸收不良)以及暴露于农药混合物中的每种物质30μg/ L的幼虫中(脊柱变形)。对孵化成功率,幼虫长度,心率或幼虫运动没有影响。在分子水平上检测到强响应,包括诱导调节细胞周期的p53基因(农药混合物-每种物质1μg/ L; MESA 30μg/ L; MOA 100μg/ L),作为cyp26a1基因编码的诱导细胞色素P450(农药混合物-每种物质1μg/ L)。与环境有关的农药混合物浓度(每种物质1μg/ L)和MESA代谢物(1μg/ L)都过度表达了与甲状腺系统调节有关的基因(dio2,thra,thrb)。斑马鱼的甲状腺系统破坏由过表达的基因以及一些相关的发育畸形(主要是膀胱和卵黄囊异常)以及自发尾巴运动的减少所揭示。从而,
更新日期:2020-02-07
中文翻译:
与环境相关的S-甲草胺及其两种代谢物的混合物会影响斑马鱼胚胎中的甲状腺代谢。
除草剂及其代谢物经常在水体中被检测到,它们可能对非目标生物造成不利影响。它们在环境相关浓度下的作用通常不清楚,特别是在农药混合物方面。因此,这项研究调查了一种最常用的除草剂:S-异丙甲草胺及其两种代谢产物,甲草胺草酸苯甲酸(MOA)和甲草胺乙磺酸(MESA)对斑马鱼胚胎(Danio rerio)发育的影响。胚胎暴露于单个物质及其与环境相关的混合物,直到120 hpf(受精后数小时)。重点放在致死性终点,例如畸形,孵化成功,幼虫长度,自发运动,心率和运动。此外,分析了与甲状腺系统破坏,氧化应激防御,线粒体代谢,细胞周期调节和视黄酸(RA)信号通路相关的八个基因的表达水平。暴露于异丙甲草胺(1μg/ L)和农药混合物(每种物质1μg/ L)会显着降低21 hpf胚胎的自发尾巴运动。很少观察到罕见的发育畸形,但是仅在暴露于100μg/ L以上的单个物质(颅面变形,未充气的气囊,卵黄囊吸收不良)以及暴露于农药混合物中的每种物质30μg/ L的幼虫中(脊柱变形)。对孵化成功率,幼虫长度,心率或幼虫运动没有影响。在分子水平上检测到强响应,包括诱导调节细胞周期的p53基因(农药混合物-每种物质1μg/ L; MESA 30μg/ L; MOA 100μg/ L),作为cyp26a1基因编码的诱导细胞色素P450(农药混合物-每种物质1μg/ L)。与环境有关的农药混合物浓度(每种物质1μg/ L)和MESA代谢物(1μg/ L)都过度表达了与甲状腺系统调节有关的基因(dio2,thra,thrb)。斑马鱼的甲状腺系统破坏由过表达的基因以及一些相关的发育畸形(主要是膀胱和卵黄囊异常)以及自发尾巴运动的减少所揭示。从而,