Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China.
Experimental Teaching Center of Public Health and Preventive Medicine, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China.
Ecotoxicol Environ Saf. 2024 Oct 1;284:116879. doi: 10.1016/j.ecoenv.2024.116879. Epub 2024 Aug 13.
Pervasive environmental pollutants, specifically particulate matter (PM), possess the potential to disrupt homeostasis of female thyroid hormone (TH). However, the precise mechanism underlying this effect remains unclear. In this study, we established a model of PM-induced thyroid damage in female rats through intratracheal instillation and employed histopathological and molecular biological methods to observe the toxic effects of PM on the thyroid gland. Transcriptome gene analysis and 16S rRNA sequencing were utilized to investigate the impact of PM exposure on the female rat thyroid gland. Furthermore, based on the PM-induced toxic model in female rats, we evaluated its effects on intestinal microbiota, TH levels, and indicators of thyroid function. The findings revealed that PM exposure induced histopathological damage to thyroid tissue by disrupting thyroid hormone levels (total T3 [TT3], (P < 0.05); total T4 [TT4], (P < 0.05); and thyrotropin hormone [TSH], (P < 0.05)) and functional indices (urine iodine [UI], P > 0.05), thus further inducing histopathological injuries. Transcriptome analysis identified differentially expressed genes (DEGs), primarily concentrated in interleukin 17 (IL-17), forkhead box O (FOXO), and other signaling pathways. Furthermore, exposure to PM altered the composition and abundance of intestinal microbes. Transcriptome and microbiome analyses demonstrated a correlation between the DEGs within these pathways and the flora present in the intestines. Moreover, 16 S rRNA gene sequencing analysis or DEGs combined with thyroid function analysis revealed that exposure to PM significantly induced thyroid hormone imbalance. We further identified key DEGs involved in thyroid function-relevant pathways, which were validated using molecular biology methods for clinical applications. In conclusion, the homeostasis of the "gut-thyroid" axis may serve as the underlying mechanism for PM-induced thyrotoxicity in female rats.
普遍存在的环境污染物，特别是颗粒物（PM），有可能破坏女性甲状腺激素（TH）的体内平衡。然而，这种影响的确切机制尚不清楚。在这项研究中，我们通过气管内滴注建立了 PM 诱导的雌性大鼠甲状腺损伤模型，并采用组织病理学和分子生物学方法观察 PM 对甲状腺的毒性作用。我们利用转录组基因分析和 16S rRNA 测序来研究 PM 暴露对雌性大鼠甲状腺的影响。此外，基于 PM 诱导的雌性大鼠毒性模型，我们评估了其对肠道微生物群、TH 水平和甲状腺功能指标的影响。研究结果表明，PM 暴露通过扰乱甲状腺激素水平（总三碘甲状腺原氨酸[TT3]，（P < 0.05）；总甲状腺素[TT4]，（P < 0.05）；和促甲状腺激素[TSH]，（P < 0.05））和功能指标（尿碘[UI]，P > 0.05），从而进一步诱导甲状腺组织的组织病理学损伤，诱导甲状腺组织的组织病理学损伤。转录组分析确定了差异表达基因（DEGs），主要集中在白细胞介素 17（IL-17）、叉头框 O（FOXO）和其他信号通路中。此外，暴露于 PM 改变了肠道微生物的组成和丰度。转录组和微生物组分析表明，这些通路中的 DEGs 与肠道中的菌群之间存在相关性。此外，16S rRNA 基因测序分析或 DEGs 与甲状腺功能分析相结合表明，PM 暴露显著诱导了甲状腺激素失衡。我们进一步确定了参与甲状腺功能相关途径的关键 DEGs，并通过分子生物学方法进行了验证，为临床应用提供了依据。总之，“肠-甲状腺”轴的体内平衡可能是 PM 诱导雌性大鼠甲状腺毒性的潜在机制。
