Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China; College of Environmental Science and Engineering, Tongji University, Shanghai, China; State Key Laboratory of Pollution Control and Resource Reuse (Tongji University), China.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117052. doi: 10.1016/j.ecoenv.2024.117052. Epub 2024 Sep 18.
PM is a complex mixture, with water-soluble inorganic ions (WSII), mainly NH, SO, and NO, constituting major components. Early-life PM exposure has been shown to induce adverse health consequence but it is difficult to determine whether such an effect occurs prenatally (preconception, gestational) or postnatally in human studies.
Four groups of C57BL/6 J mice were assigned to four exposure conditions: PM NO, PM SO, PM NH and clean air, and exposure started at 4 weeks old. At 8 weeks old, mice bred within group. The exposure continued during gestation. After delivery, both the maternal and F mice (offspring) were kept in clean air without exposure to PM. Respiratory function and pulmonary pathology were assessed in offspring mice at 8 weeks of age. In parallel, placenta tissue was collected for transcriptome profiling and mechanistic investigation.
F mice in PM NH, SO and NO groups had 32.2 % (p=6.0e-10), 30.3 % (p=3.8e-10) and 16.9 % (p=5.7e-8) lower peak expiratory flow (PEF) than the clean air group. Importantly, the exposure-induced lung function decline was greater in male than female offspring. Moreover, exposure to PM WSII before conception and during gestation was linked to increased airway wall thickness and elevated pulmonary neutrophil and macrophage counts in the offspring mice. At the molecular level, the exposure significantly disrupted gene expression in the placenta, affecting crucial functional pathways related to sex hormone response and inflammation.
PM WSII exposure during preconception and gestational period alone without post-natal exposure substantially impacted offspring's respiratory function as measured at adolescent age. Our results support the paradigm of fetal origin of environmentally associated chronic lung disease and highlight sex differences in susceptibility to air pollution exposure.
PM 是一种复杂的混合物，水溶性无机离子（WSII）主要包括 NH、SO 和 NO，构成主要成分。早期 PM 暴露已被证明会导致不良健康后果，但在人类研究中，很难确定这种影响是在产前（受孕前、妊娠期）还是产后发生的。
将 4 组 C57BL/6J 小鼠分配到 4 种暴露条件下：PM NO、PM SO、PM NH 和清洁空气，并从 4 周龄开始暴露。8 周龄时，组内繁殖。暴露在妊娠期继续进行。分娩后，母体和 F 代小鼠（后代）均在清洁空气中生活，不接触 PM。在 8 周龄时评估后代小鼠的呼吸功能和肺部病理学。同时，收集胎盘组织进行转录组谱分析和机制研究。
PM NH、SO 和 NO 组的 F 代小鼠的呼气峰流速（PEF）比清洁空气组分别低 32.2%（p=6.0e-10）、30.3%（p=3.8e-10）和 16.9%（p=5.7e-8）。重要的是，雄性后代的暴露引起的肺功能下降比雌性后代更大。此外，受孕前和妊娠期暴露于 PM WSII 与后代小鼠气道壁厚度增加和肺部中性粒细胞和巨噬细胞计数升高有关。在分子水平上，暴露显著扰乱了胎盘的基因表达，影响了与性激素反应和炎症相关的关键功能途径。
仅在受孕前和妊娠期暴露于 PM WSII 而没有产后暴露，就会对青少年时期的后代呼吸功能产生重大影响。我们的结果支持了环境相关慢性肺部疾病的胎儿起源假说，并强调了对空气污染暴露的易感性存在性别差异。
