Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Public Health Program, School of Exercise and Sport Science, University of Mary Hardin-Baylor, Belton, TX, USA.
Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Toxicol Lett. 2023 Jul 1;383:17-32. doi: 10.1016/j.toxlet.2023.05.011. Epub 2023 May 26.
Prenatal arsenic exposure is a major public health concern, associated with altered birth outcomes and increased respiratory disease risk. However, characterization of the long-term effects of mid-pregnancy (second trimester) arsenic exposure on multiple organ systems is scant. This study aimed to characterize the long-term impact of mid-pregnancy inorganic arsenic exposure on the lung, heart, and immune system, including infectious disease response using the C57BL/6 mouse model. Mice were exposed from gestational day 9 till birth to either 0 or 1000 µg/L sodium (meta)arsenite in drinking water. Male and female offspring assessed at adulthood (10-12 weeks of age) did not show significant effects on recovery outcomes after ischemia reperfusion injury but did exhibit increased airway hyperresponsiveness compared to controls. Flow cytometric analysis revealed significantly greater total numbers of cells in arsenic-exposed lungs, lower MHCII expression in natural killer cells, and increased percentages of dendritic cell populations. Activated interstitial (IMs) and alveolar macrophages (AMs) isolated from arsenic-exposed male mice produced significantly less IFN-γ than controls. Conversely, activated AMs from arsenic-exposed females produced significantly more IFN-γ than controls. Although systemic cytokine levels were higher upon Mycobacterium tuberculosis (Mtb) infection in prenatally arsenic-exposed offspring there was no difference in lung Mtb burden compared to controls. This study highlights significant long-term impacts of prenatal arsenic exposure on lung and immune cell function. These effects may contribute to the elevated risk of respiratory diseases associated with prenatal arsenic exposure in epidemiology studies and point to the need for more research into mechanisms driving these maintained responses.
产前砷暴露是一个主要的公共卫生问题，与出生结果改变和呼吸道疾病风险增加有关。然而，描述妊娠中期（第二孕期）砷暴露对多个器官系统的长期影响的研究甚少。本研究旨在使用 C57BL/6 小鼠模型来描述妊娠中期无机砷暴露对肺、心脏和免疫系统的长期影响，包括对传染病反应的影响。从妊娠第 9 天到出生，小鼠被暴露于饮用水中的 0 或 1000μg/L 亚砷酸钠中。在成年期（10-12 周龄）评估的雄性和雌性后代在缺血再灌注损伤后的恢复结果上没有显示出显著影响，但与对照组相比，它们表现出更高的气道高反应性。流式细胞术分析显示，砷暴露的肺部中总细胞数量显著增加，自然杀伤细胞中的 MHCII 表达降低，树突状细胞群体的百分比增加。从砷暴露的雄性小鼠中分离出的活化的间质性（IM）和肺泡巨噬细胞（AMs）产生的 IFN-γ 明显少于对照组。相反，从砷暴露的雌性小鼠中分离出的活化 AM 产生的 IFN-γ 明显多于对照组。尽管在产前砷暴露的后代感染结核分枝杆菌（Mtb）后系统性细胞因子水平升高，但与对照组相比，肺 Mtb 负担没有差异。本研究强调了产前砷暴露对肺和免疫细胞功能的长期影响。这些影响可能导致流行病学研究中与产前砷暴露相关的呼吸道疾病风险增加，并指出需要更多研究来探讨驱动这些持续反应的机制。
