Perfluorobutanesulfonic acid (PFBS), a short-chain alternative to perfluorooctanesulfonic acid (PFOS), is widely used in various products and is increasingly present in environmental media and human bodies. Recent epidemiological findings have raised concerns about its potential adverse health effects, although the specific toxic mechanism remains unclear. This study aimed to investigate the metabolic toxicity of gestational PFBS exposure in maternal rats. Pregnant Sprague Dawley (SD) rats were randomly assigned to three groups and administered either 3% starch gel (control), 5, or 50 mg/kg bw·d PFBS. Oral glucose tolerance tests (OGTT) and lipid profiles were measured, and integrated omics analysis (transcriptomics and non-targeted metabolomics) was employed to identify changes in genes and metabolites and their relationships with metabolic phenotypes. The results revealed that rats exposed to 50 mg/kg bw·d PFBS exhibited a significant decrease in 1-h glucose levels and the area under the curve (AUC) of OGTT compared with the starch group. Transcriptomics analysis indicated significant alterations in gene expression related to cytochrome P450 exogenous metabolism, glutathione metabolism, bile acid secretion, tumor pathways, and retinol metabolism. Differentially expressed metabolites (DEMs) were enriched in pathways such as pyruvate metabolism, the glucagon signaling pathway, central carbon metabolism in cancer, and the citric acid cycle. Co-enrichment analysis and pairwise correlation analysis among genes, metabolites, and outcomes identified several differentially expressed genes (DEGs), including , , , , , , and DEMs such as fumaric acid, L-lactic acid, 4-hydroxynonenal, and acetylvalerenolic acid. These DEGs and DEMs may play a role in the modulation of glucolipid metabolic pathways. In conclusion, our results suggest that gestational exposure to PFBS may induce molecular perturbations in glucose homeostasis. These findings provide insights into the potential mechanisms contributing to the heightened risk of abnormal glucose tolerance associated with PFBS exposure.

中文翻译：

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多组学揭示暴露于短链全氟丁磺酸的妊娠大鼠葡萄糖稳态紊乱


全氟丁磺酸（PFBS）是全氟辛烷磺酸（PFOS）的短链替代品，广泛应用于各种产品中，并且越来越多地存在于环境介质和人体中。尽管具体的毒性机制尚不清楚，但最近的流行病学研究结果引起了人们对其潜在不利健康影响的担忧。本研究旨在探讨妊娠期 PFBS 暴露对母鼠的代谢毒性。怀孕的 Sprague Dawley (SD) 大鼠被随机分为三组，并给予 3% 淀粉凝胶（对照）、5 或 50mg/kg bw·d PFBS。测量口服葡萄糖耐量试验（OGTT）和血脂谱，并采用综合组学分析（转录组学和非靶向代谢组学）来识别基因和代谢物的变化及其与代谢表型的关系。结果显示，与淀粉组相比，暴露于50mg/kg bw·d PFBS的大鼠1小时血糖水平和OGTT曲线下面积（AUC）显着降低。转录组学分析表明与细胞色素 P450 外源代谢、谷胱甘肽代谢、胆汁酸分泌、肿瘤途径和视黄醇代谢相关的基因表达发生显着变化。差异表达代谢物（DEM）富含丙酮酸代谢、胰高血糖素信号传导途径、癌症中的中心碳代谢和柠檬酸循环等途径。基因、代谢物和结果之间的共富集分析和成对相关分析确定了几个差异表达基因 (DEG)，包括 、 、 、 、 、 和 DEM，例如富马酸、L-乳酸、4-羟基壬烯醛和乙酰戊烯酸。 这些 DEG 和 DEM 可能在糖脂代谢途径的调节中发挥作用。总之，我们的结果表明，妊娠期接触 PFBS 可能会引起葡萄糖稳态的分子扰动。这些发现提供了对导致与 PFBS 暴露相关的异常葡萄糖耐量风险增加的潜在机制的见解。