妊娠期全氟辛烷磺酸暴露通过影响后代大鼠的免疫上皮串扰诱导肺泡发育缺陷

摘要(中文译文)

全氟辛烷磺酸（PFOS）是一种环境内分泌干扰物，孕期暴露可对子代肺发育产生不良影响。然而，其潜在的细胞和分子机制尚未完全阐明。在本研究中，从妊娠第11天至第20天对母鼠经口给予PFOS（0.1 mg/kg体重），并在出生后第0、7、14和21天评估子代肺组织。结果表明，孕期PFOS暴露诱导了支气管肺发育不良（BPD）样病理改变，其特征为肺泡结构简化、糖原潴留和胶原沉积。对新生大鼠肺组织的单细胞RNA测序分析显示，PFOS深刻重塑了肺细胞图谱，导致过渡型肺泡上皮II型细胞（AECIIs）显著积聚，并使肺泡巨噬细胞向促炎和促纤维化表型偏移。细胞间通讯分析表明，来源于单核细胞和肺泡巨噬细胞的分子，包括FN1-CD44轴，可能是导致上皮缺陷的主要信号。总体而言，这些发现确定了AECII分化障碍是肺泡发育缺陷的关键事件，并为免疫-上皮细胞串扰在PFOS诱导的肺毒性中的作用提供了新的见解。

Abstract

Perfluorooctane sulfonate (PFOS), an environmental endocrine-disrupting compound, can adversely affect offspring lung development following gestational exposures. However, the underlying cellular and molecular mechanisms have yet to be fully elucidated. In our research, dams were orally administered PFOS (0.1 mg/kg BW) from gestational days 11 to 20, and the offspring lungs were assessed at postnatal days 0, 7, 14, and 21. It was shown that gestational PFOS exposure induced bronchopulmonary dysplasia (BPD)-like pathology, characterized by simplified alveolar structure, glycogen retention, and collagen deposition. Single-cell RNA sequencing analysis of newborn rat lungs revealed that PFOS profoundly remodeled the pulmonary cellular landscape, resulting in a pronounced accumulation of transitional alveolar epithelial type II cells (AECIIs), and a shift of alveolar macrophages toward pro-inflammatory and pro-fibrotic phenotypes. Intercellular communication analysis indicated that molecules originating from monocytes and alveolar macrophages, including the FN1-CD44 axis, may be the major signals responsible for epithelial defects. Overall, these findings identify the disruption of AECII differentiation as a pivotal event in alveolar developmental defects and provide novel insights into the role of immune-epithelial crosstalk in PFOS-induced pulmonary toxicity.

如何引用

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