The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne 3052, VIC, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, VIC, Australia.
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, VIC, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Parkville 3052, VIC, Australia.
Cell Rep. 2020 Apr 28;31(4):107573. doi: 10.1016/j.celrep.2020.107573.
Germline epigenetic factors influence transgenerational inheritance of behavioral traits upon changes in experience and environment. Immune activation due to infection can also modulate brain function, but whether this experience can be passed down to offspring remains unknown. Here, we show that infection of the male lineage with the common human parasite Toxoplasma results in transgenerational behavioral changes in offspring in a sex-dependent manner. Small RNA sequencing of sperm reveals significant transcriptional differences of infected animals compared to controls. Zygote microinjection of total small RNA from sperm of infected mice partially recapitulates the behavioral phenotype of naturally born offspring, suggesting an epigenetic mechanism of behavioral inheritance in the first generation. Our results demonstrate that sperm epigenetic factors can contribute to intergenerational inheritance of behavioral changes after pathogenic infection, which could have major public health implications.
种系表观遗传因素影响行为特征的跨代遗传，使其在经验和环境变化时发生改变。感染导致的免疫激活也可以调节大脑功能，但这种经验是否可以传递给后代尚不清楚。在这里，我们表明，雄性谱系感染常见的人类寄生虫弓形虫会导致后代出现以性别依赖方式的跨代行为变化。与对照组相比，受感染动物精子的小 RNA 测序显示出明显的转录差异。来自受感染小鼠精子的总小 RNA 的受精卵微注射部分再现了自然出生后代的行为表型，这表明在第一代中存在行为遗传的表观遗传机制。我们的研究结果表明，精子表观遗传因素可能有助于在病原感染后行为变化的跨代遗传，这可能具有重大的公共卫生意义。
