Sex differences in the incidence and prognosis of respiratory diseases have been reported. Studies have shown that women are at increased risk of adverse health outcomes from air pollution than men, but sex-specific immune gene expression patterns and regulatory networks have not been well studied in the lung. MicroRNAs (miRNAs) are environmentally sensitive posttranscriptional regulators of gene expression that may mediate the damaging effects of inhaled pollutants in the lung, by altering the expression of innate immunity molecules. Here, male and female mice of the C57/Bl6 background were exposed to 2ppm of ozone or filtered air (control) for 3 hours. Female mice were also exposed at different stages of the estrous cycle. Following exposure, lungs were harvested and total RNA was extracted. We used PCR arrays to study sex-differences in the expression of 84 miRNAs predicted to target inflammatory and immune genes. Our results identified differentially expressed miRNA signatures in the lungs of male vs. female exposed to ozone. In silico pathway analyses identified sex-specific biological networks affected by exposure to ozone that ranged from direct predicted gene targeting to complex interactions with multiple intermediates. We also identified differences in miRNA expression and predicted regulatory networks in females exposed to ozone at different estrous cycle stages. These results indicate that both sex and hormonal status can influence lung miRNA expression in response to ozone exposure, indicating that sex-specific miRNA regulation of inflammatory gene expression could mediate differential pollution-induced health outcomes in men and women.
Overall design
Male and female C57BL/6 mice of 8 weeks of age were exposed to 2ppm ozone (O3) or filtered air (FA) for 3 hours. Females were exposed at different stages of the estrous cycle: diestrus 1 (D1), diestrus 2 (D2), proestrus (P), estrus (E). Total RNA was extracted from whole lung homogenates and PCR arrays were used to determine the expression of 84 miRNAs associated with inflammation and immunity (3-9 animals per condition).
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