Combined transcriptome and microbiome analysis reveals the thyrotoxic effects of PM2.5 in female rats

Xinwen Dong; Xiaofeng Han; Sanqiao Yao; Yaguang Su; Zheng Luo; Lvfei Deng; Fengquan Zhang; Jie Xu; Li Zhang; Haibin Li; Weidong Wu

doi:10.1016/j.ecoenv.2024.116879

Combined transcriptome and microbiome analysis reveals the thyrotoxic effects of PM_2.5 in female rats

Ecotoxicol Environ Saf. 2024 Oct 1:284:116879. doi: 10.1016/j.ecoenv.2024.116879. Epub 2024 Aug 13.

Authors

Xinwen Dong¹, Xiaofeng Han², Sanqiao Yao³, Yaguang Su⁴, Zheng Luo⁵, Lvfei Deng⁶, Fengquan Zhang⁷, Jie Xu⁸, Li Zhang⁹, Haibin Li¹⁰, Weidong Wu¹¹

Affiliations

¹ Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: dongxinwen118@yeah.net.
² Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 50220102001@stu.xxmu.edu.cn.
³ Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 131059@xxmu.edu.cn.
⁴ Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 50220209007@stu.xxmu.edu.cn.
⁵ Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: lz15603741558@163.com.
⁶ Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 50210102038@stu.xxmu.edu.cn.
⁷ Experimental Teaching Center of Public Health and Preventive Medicine, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: zhangfengquan29@126.com.
⁸ Experimental Teaching Center of Public Health and Preventive Medicine, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: sunny224802@163.com.
⁹ Center for Bioinformatics and Statistical Health Research, School of Public Health, Xinxiang Medical, Xinxiang, Henan Province 453003, China. Electronic address: zhangli@xxmu.edu.cn.
¹⁰ Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: Lihaibin@xxmu.edu.cn.
¹¹ Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: wuwridong@xxmu.edu.cn.

PMID: 39142117
DOI: 10.1016/j.ecoenv.2024.116879

Abstract

Pervasive environmental pollutants, specifically particulate matter (PM_2.5), 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_2.5-induced thyroid damage in female rats through intratracheal instillation and employed histopathological and molecular biological methods to observe the toxic effects of PM_2.5 on the thyroid gland. Transcriptome gene analysis and 16S rRNA sequencing were utilized to investigate the impact of PM_2.5 exposure on the female rat thyroid gland. Furthermore, based on the PM_2.5-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_2.5 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_2.5 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_2.5 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_2.5-induced thyrotoxicity in female rats.

Keywords: Female rats; Microbiota; PM(2.5); Pearson correlation analysis; RNA-seq; Thyrotoxicity.

MeSH terms

Air Pollutants / toxicity
Animals
Female
Gastrointestinal Microbiome / drug effects
Particulate Matter* / toxicity
RNA, Ribosomal, 16S
Rats
Rats, Sprague-Dawley
Thyroid Gland* / drug effects
Thyroid Gland* / pathology
Thyroid Hormones
Transcriptome* / drug effects

Substances

Particulate Matter
Thyroid Hormones
Air Pollutants
RNA, Ribosomal, 16S