School of Public Health, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of study on abnormal gametes and reproductive tract, No 81 Meishan Road, Hefei, Anhui, China.
School of Public Health, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China.
Ecotoxicol Environ Saf. 2021 Oct 15;223:112565. doi: 10.1016/j.ecoenv.2021.112565. Epub 2021 Aug 3.
The impairments of maternal fenvalerate exposure have been well documented in previous study, but little was known about the effects of paternal fenvalerate exposure. The current study aimed to assess the effects of paternal fenvalerate exposure on spatial cognition and hippocampus across generations. Adult male mice (F0) were orally administered with fenvalerate (0, 2 or 20 mg/kg) for 5 weeks. F0 males were mated with untreated-females to generate F1 generation. F1 males were mated with F1 control females to generate F2 generation. For F1 and F2 adult offspring, spatial learning and memory were detected by Morris water maze. Results showed that spatial learning and memory were impaired in F1 females but not F1 males derived from F0 males exposed to 20 mg/kg FEN. Furthermore, significant impairment of spatial learning and memory were found in F2 females but not F2 males derived from F0 males exposed to 20 mg/kg FEN. As expected, histopathology showed that neural density in hippocampal CA3 region was reduced in F1 and F2 females but not F1 and F2 males derived from F0 males exposed to 20 mg/kg FEN. Mechanistically, hippocampal thyroid hormone receptor alpha1 (TRα1) was down-regulated in F1 and F2 females derived from F0 males exposed to 20 mg/kg FEN. Correspondingly, hippocampal brain-derived neurotrophic factor, tropomyosin receptor kinase B and p75 neurotrophin receptor, three downstream genes of TR signaling, were down-regulated in F1 and F2 females. Taken together, the present study firstly found that paternal fenvalerate exposure transgenerationally impaired spatial cognition in a gender-dependent manner. Hippocampal TR signaling may, at least partially, contribute to the process of cognitive impairment induced by paternal fenvalerate exposure. Further exploration in the mode of action of fenvalerate is critically important to promote human health and environmental safety.
母体氰戊菊酯暴露的损伤在以前的研究中已有充分记录，但对于父体氰戊菊酯暴露的影响知之甚少。本研究旨在评估父体氰戊菊酯暴露对跨代空间认知和海马体的影响。成年雄性小鼠（F0）经口给予氰戊菊酯（0、2 或 20mg/kg）5 周。F0 雄性与未处理的雌性交配，产生 F1 代。F1 雄性与 F1 对照雌性交配，产生 F2 代。对 F1 和 F2 成年后代进行 Morris 水迷宫检测空间学习和记忆。结果显示，来自暴露于 20mg/kg 氰戊菊酯的 F0 雄性的 F1 雌性空间学习和记忆受损，但 F1 雄性不受影响。此外，来自暴露于 20mg/kg 氰戊菊酯的 F0 雄性的 F2 雌性空间学习和记忆受损，但 F2 雄性不受影响。正如预期的那样，组织病理学显示，来自暴露于 20mg/kg 氰戊菊酯的 F0 雄性的 F1 和 F2 雌性海马 CA3 区神经密度降低，但 F1 和 F2 雄性不受影响。在机制上，来自暴露于 20mg/kg 氰戊菊酯的 F0 雄性的 F1 和 F2 雌性海马甲状腺激素受体 α1（TRα1）下调。相应地，来自暴露于 20mg/kg 氰戊菊酯的 F0 雄性的 F1 和 F2 雌性海马脑源性神经营养因子、原肌球蛋白受体激酶 B 和 p75 神经营养素受体这三个 TR 信号下游基因下调。总之，本研究首次发现父体氰戊菊酯暴露以性别依赖的方式跨代损害空间认知。海马 TR 信号可能至少部分参与了父体氰戊菊酯暴露诱导的认知损伤过程。进一步探索氰戊菊酯的作用模式对于促进人类健康和环境安全至关重要。
