There is no safe level of air pollution for human health. Traffic-related particulate matter (PM2.5) is a major in-utero toxin, mechanisms of action of which are not fully understood. BALB/c dams were exposed to an Australian level of traffic PM2.5 (5 µg/mouse/day, intranasal, 6 weeks before mating, during gestation and lactation). Male offspring had reduced memory in adulthood, whereas memory was normal in female littermates, similar to human responses. Maternal PM2.5 exposure resulted in oxidative stress and abnormal mitochondria in male, but not female, brains. RNA-sequencing analysis showed unique sex-related changes in newborn brains. Two X-chromosome-linked histone lysine demethylases, Kdm6a and Kdm5c, demonstrated higher expression in female compared to male littermates, in addition to upregulated genes with known functions to support mitochondrial function, synapse growth and maturation, cognitive function, and neuroprotection. No significant changes in Kdm6a and Kdm5c were found in male littermates, nor other genes, albeit significantly impaired memory function after birth. In primary foetal cortical neurons, PM2.5 exposure suppressed neuron and synaptic numbers and induced oxidative stress, which was prevented by upregulation of Kdm6a or Kdm5c. Therefore, timely epigenetic adaptation by histone demethylation to open DNA for translation before birth may be the key to protecting females against prenatal PM2.5 exposure-induced neurological disorders, which fail to occur in males associated with their poor cognitive outcomes.

中文翻译：

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母亲长期接触低剂量 PM2.5 会以性别依赖性方式影响认知结果


对于人类健康来说，空气污染不存在安全水平。交通相关颗粒物 (PM2.5) 是一种主要的子宫内毒素，其作用机制尚不完全清楚。 BALB/c 母鼠暴露于澳大利亚交通 PM2.5 水平（5 µg/小鼠/天，鼻内，交配前 6 周、妊娠和哺乳期间）。雄性后代在成年后记忆力下降，而雌性后代的记忆力则正常，与人类的反应相似。母亲接触 PM2.5 会导致男性（而非女性）大脑氧化应激和线粒体异常。 RNA测序分析显示新生儿大脑中存在独特的与性别相关的变化。两种 X 染色体连接的组蛋白赖氨酸脱甲基酶 Kdm6a 和 Kdm5c 在雌性同窝雄性中表现出更高的表达，此外，具有支持线粒体功能、突触生长和成熟、认知功能和神经保护功能的已知功能的基因上调。尽管出生后记忆功能显着受损，但雄性同窝小鼠的 Kdm6a 和 Kdm5c 以及其他基因均未发现显着变化。在初级胎儿皮质神经元中，PM2.5 暴露会抑制神经元和突触数量并诱导氧化应激，而氧化应激可通过上调 Kdm6a 或 Kdm5c 来预防。因此，通过组蛋白去甲基化及时进行表观遗传适应，在出生前打开 DNA 进行翻译，可能是保护女性免受产前 PM2.5 暴露引起的神经系统疾病的关键，而男性则不会发生这种疾病，而这与认知结果不佳有关。