Chronic maternal exposure to low-dose PM2.5 impacts cognitive outcomes in a sex-dependent manner

Autor: Brian G Oliver, Xiaomin Huang, Rochelle Yarak, Xu Bai, Qi Wang, Razia Zakarya, Karosham D. Reddy, Chantal Donovan, Richard Y. Kim, James Morkaya, Baoming Wang, Yik Lung Chan, Sonia Saad, Alen Faiz, David van Reyk, Alexei Verkhratsky, Chenju Yi, Hui Chen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Environment International, Vol 191, Iss , Pp 108971- (2024)
Druh dokumentu: article
ISSN: 0160-4120
DOI: 10.1016/j.envint.2024.108971
Popis: 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.
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