Department of Pediatrics, Peking University First Hospital, No.1 Xi'an Men Street, West District, Beijing, 100034, China; Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Department of Pediatrics, Peking University First Hospital, No.1 Xi'an Men Street, West District, Beijing, 100034, China.
Environ Pollut. 2021 Mar 1;272:115535. doi: 10.1016/j.envpol.2020.115535. Epub 2020 Aug 28.
Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant widely used in industry and consumer products. Previous studies with rats suggested that gestational exposure to PFOS may affect the lung development in the offspring. The mechanism, however, is still unknown. In the present study, we have exposed 24 pregnant SD rats from gestational day 12-18 to different doses of PFOS (0, 1 or 5 mg/kg BW/day). The lungs of the offspring were analyzed at postnatal days 1, 3, 7 and 14. PFOS treatment appeared to reduce the alveolar numbers, resulting in simplified alveolar structure and thickened alveolar septa. Also, PFOS treated animals had increased lung inflammation with up-regulated inflammasome associated proteins NLRP3, ASC, Caspase-1 and GSDMD and increased inflammatory cytokines IL-18 and IL-1β. At the same time, HIF-1α and VEGFA were significantly down-regulated. Since HIF-1α and VEGFA are critical factors promoting alveolar development and pulmonary angiogenesis, these results suggested that PFOS may also affect lung development by inhibiting HIF-1α and VEGFA expression. Our results here indicate that gestational exposure to PFOS may affect lung development in the offspring with pathological characteristics similar to bronchopulmonary dysplasia (BPD), a severe lung developmental defect. The results also suggest that environmental factors such as PFOS may contribute to the increasing incidence of developmental lung diseases, such as BPD, by elevating lung inflammation and inhibiting lung development.
全氟辛烷磺酸 (PFOS) 是一种广泛应用于工业和消费产品的人造氟表面活性剂。先前对大鼠的研究表明，妊娠期接触 PFOS 可能会影响后代的肺部发育。然而，其机制尚不清楚。在本研究中，我们从妊娠第 12 天至 18 天开始，用不同剂量的 PFOS（0、1 或 5mg/kg BW/day）对 24 只怀孕的 SD 大鼠进行了暴露。在出生后第 1、3、7 和 14 天分析了后代的肺部。PFOS 处理似乎减少了肺泡数量，导致肺泡结构简化和肺泡隔增厚。此外，PFOS 处理的动物肺部炎症增加，与炎症小体相关的蛋白 NLRP3、ASC、Caspase-1 和 GSDMD 上调，促炎细胞因子 IL-18 和 IL-1β增加。同时，HIF-1α 和 VEGFA 显著下调。由于 HIF-1α 和 VEGFA 是促进肺泡发育和肺血管生成的关键因素，这些结果表明，PFOS 也可能通过抑制 HIF-1α 和 VEGFA 的表达来影响肺部发育。我们的研究结果表明，妊娠期接触 PFOS 可能会影响后代的肺部发育，其病理特征类似于支气管肺发育不良（BPD），这是一种严重的肺部发育缺陷。研究结果还表明，PFOS 等环境因素可能通过提高肺部炎症和抑制肺部发育，导致发育性肺部疾病（如 BPD）的发病率上升。
