Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, North Carolina.
Oak Ridge Institute for Science and Education, Research Triangle Park, North Carolina.
Am J Pathol. 2024 Sep;194(9):1636-1663. doi: 10.1016/j.ajpath.2024.05.013.
Air pollution exposure during pregnancy may affect fetal growth. Fetal growth restriction (FGR) is associated with reduced lung function in children that can persist into adulthood. Using an established model of asymmetrical FGR in Long-Evans rats, this study investigated sex differences in effects of early life ozone exposure on lung development and maturation. Adverse health effects for i) gestational exposure (with impacts on primary alveolarization), ii) peri-adolescent exposure (with impacts on secondary alveolarization), and iii) cumulative exposure across both periods were evaluated. Notably, female offspring were most affected by gestational ozone exposure, likely because of impaired angiogenesis and corresponding decreases in primary alveolarization. Females had diminished lung capacity, fewer mature alveoli, and medial hypertrophy of small and large pulmonary arteries. Males, especially FGR-prone offspring, were more affected by peri-adolescent ozone exposure. Males had increased ductal areas, likely due to disrupted secondary alveolarization. Altered lung development may increase risk of developing diseases, such as pulmonary arterial hypertension or chronic obstructive pulmonary disease. Pulmonary arterial hypertension disproportionately affects women. In the United States, chronic obstructive pulmonary disease prevalence is increasing, especially in women; and prevalence for both men and women is highest in urbanized areas. This investigation underlines the importance of evaluating results separately by sex, and provides biologic plausibility for later consequences of early-life exposure to ozone, a ubiquitous urban air pollutant.
孕期接触空气污染可能会影响胎儿生长。胎儿生长受限（FGR）与儿童肺功能下降有关，这种下降在成年后仍会持续存在。本研究采用长耳大白鼠不对称性 FGR 已有模型，调查了孕期早期暴露于臭氧对肺发育和成熟的影响在性别上的差异。评估了 i）孕期暴露（对初级肺泡化产生影响）、ii）青春期前暴露（对次级肺泡化产生影响）和 iii）两个时期的累积暴露对健康的不利影响。值得注意的是，妊娠臭氧暴露对雌性后代的影响最大，这可能是由于血管生成受损，导致初级肺泡化相应减少。雌性后代的肺容量减少，成熟肺泡数量减少，小、大肺动脉中层肥厚。雄性，尤其是易发生 FGR 的雄性后代，更容易受到青春期前臭氧暴露的影响。雄性后代的导管区域增加，可能是由于次级肺泡化受到干扰。肺部发育的改变可能会增加患疾病的风险，如肺动脉高压或慢性阻塞性肺疾病。肺动脉高压对女性的影响更为严重。在美国，慢性阻塞性肺疾病的患病率正在上升，尤其是在女性中；而在城市地区，男性和女性的患病率都最高。这项研究强调了按性别分别评估结果的重要性，并为早期暴露于臭氧（一种普遍存在的城市空气污染物）对以后的后果提供了生物学依据。
