Alteration in mRNA expression in hippocampus and next-generation effects due to paternal exposure to the neonicotinoid pesticide clothianidin

Accumulating evidence suggests that paternal environmental factors have epigenetic effects on sperm and influence offspring. Neonicotinoid pesticides, which are widely used around the world, are known to affect offspring phenotypes through maternal exposure in mice, but the effect of the paternal exposure remains unknown.The main purpose of this study was to estimate the neurobehavioral effects on offspring mice resulting from paternal exposure to the neonicotinoid pesticide clothianidin (CLO).Hippocampal RNA sequence data revealed that paternal CLO exposure altered the expression of genes related to the nervous system in male offspring, affecting pathways such as axonal guidance signaling, synaptogenesis signaling pathway, and calcium signaling. To understand the mechanisms of paternal exposure to a neonicotinoid pesticide clothianidin (CLO) to the next generation, male C57BL/6N mice were administered the non-observed-adverse-effect level (NOAEL) of CLO (50 mg/kg/day). The mRNA in hippocampus was purified and analyzed by RNA-seq.

越来越多的研究证据表明，父代环境因素可对精子产生表观遗传（epigenetic）调控效应，并对子代个体造成影响。新烟碱类杀虫剂（neonicotinoid pesticides）在全球范围内被广泛施用，已有研究证实母代暴露于该类杀虫剂可改变小鼠的子代表型，但父代暴露所产生的效应仍未明确。本研究的核心目的为评估父代暴露于新烟碱类杀虫剂噻虫胺（clothianidin，CLO）后，对子代小鼠产生的神经行为学影响。海马体（hippocampus）的RNA测序数据显示，父代暴露于CLO可改变雄性子代小鼠体内神经系统相关基因的表达，并影响轴突导向信号通路、突触发生信号通路以及钙信号通路等多条信号通路。为阐明父代暴露于新烟碱类杀虫剂噻虫胺（CLO）对其子代产生影响的分子机制，研究人员对雄性C57BL/6N小鼠施用了该药物的未观察到有害作用水平（non-observed-adverse-effect level，NOAEL）剂量（50 mg/kg/天），随后提取海马体中的mRNA并通过RNA-seq进行分析。