Mourikes Vasiliki E, Santacruz Márquez Ramsés, Deviney Ashley, Neff Alison M, Laws Mary J, Flaws Jodi A
Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA.
Toxics. 2023 Apr 7;11(4):349. doi: 10.3390/toxics11040349.
Imidacloprid is a neonicotinoid pesticide used in large-scale agricultural systems, home gardens, and veterinary pharmaceuticals. Imidacloprid is a small molecule that is more water-soluble than other insecticides, increasing the likelihood of large-scale environmental accumulation and chronic exposure of non-targeted species. Imidacloprid can be converted to the bioactive metabolite desnitro-imidacloprid in the environment and body. Little is known about the mechanisms by which imidacloprid and desnitro-imidacloprid induce ovarian toxicity. Thus, we tested the hypothesis that imidacloprid and desnitro-imidacloprid differentially affect antral follicle growth and steroidogenesis in vitro. Antral follicles were dissected from the ovaries of CD-1 mice and cultured in media containing vehicle control or 0.2 µg/mL-200 µg/mL of imidacloprid or desnitro-imidacloprid for 96 h. Follicle morphology was monitored, and follicle size was measured every 24 h. At the end of the culture periods, media were used to quantify follicular hormone levels, and follicles were used for gene expression analysis of steroidogenic regulators, hormone receptors, and apoptotic factors. Imidacloprid did not affect follicle growth or morphology compared to the control. Desnitro-imidacloprid inhibited follicle growth and caused follicles to rupture in culture compared to the control. Imidacloprid increased progesterone, whereas desnitro-imidacloprid decreased testosterone and progesterone compared to the control. Desnitro-imidacloprid also changed estradiol compared to the control. At 48 h, IMI decreased the expression of , , , , and and increased the expression of , , , and compared to the control. IMI also changed the expression of compared to the control. At 48 h, DNI decreased the expression of , , , , and and increased the expression of , , and compared to the control. At 72 h of culture, IMI significantly decreased the expression of and increased the expression of and compared to the control. At 72 h, DNI significantly decreased the expression of , , , and and increased the expression of and . At 96 h, IMI decreased the expression of , , , , and compared to the control. At 96 h, DNI decreased the expression of , , and and increased the expression of , , and compared to the control. Together, these data suggest mouse antral follicles are targets of neonicotinoid toxicity, and the mechanisms of toxicity differ between parent compounds and metabolites.
吡虫啉是一种用于大规模农业系统、家庭花园和兽用药品中的新烟碱类杀虫剂。吡虫啉是一种小分子，比其他杀虫剂更易溶于水，增加了在环境中大规模积累以及非目标物种长期接触的可能性。吡虫啉在环境和体内可转化为具有生物活性的代谢物去硝基吡虫啉。关于吡虫啉和去硝基吡虫啉诱导卵巢毒性的机制知之甚少。因此，我们测试了这样一个假设，即吡虫啉和去硝基吡虫啉在体外对腔前卵泡生长和类固醇生成有不同影响。从CD-1小鼠的卵巢中分离出腔前卵泡，并在含有溶剂对照或0.2μg/mL - 200μg/mL吡虫啉或去硝基吡虫啉的培养基中培养96小时。监测卵泡形态，每24小时测量卵泡大小。在培养期结束时，用培养基定量卵泡激素水平，卵泡用于类固醇生成调节因子、激素受体和凋亡因子的基因表达分析。与对照组相比，吡虫啉不影响卵泡生长或形态。与对照组相比，去硝基吡虫啉抑制卵泡生长并导致培养中的卵泡破裂。与对照组相比，吡虫啉增加孕酮水平，而去硝基吡虫啉降低睾酮和孕酮水平。与对照组相比，去硝基吡虫啉也改变了雌二醇水平。在48小时时，与对照组相比，吡虫啉降低了 、 、 、 和 的表达，并增加了 、 、 和 的表达。与对照组相比，吡虫啉还改变了 的表达。在48小时时，与对照组相比，去硝基吡虫啉降低了 、 、 、 和 的表达，并增加了 、 和 的表达。在培养72小时时，与对照组相比，吡虫啉显著降低了 的表达，并增加了 和 的表达。在72小时时，去硝基吡虫啉显著降低了 、 、 和 的表达，并增加了 和 的表达。在96小时时，与对照组相比，吡虫啉降低了 、 、 、 和 的表达。在96小时时，与对照组相比，去硝基吡虫啉降低了 、 和 的表达，并增加了 、 和 的表达。总之，这些数据表明小鼠腔前卵泡是新烟碱类毒性的靶点，母体化合物和代谢物的毒性机制不同。
