Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicity
Fine particulate matter (PM2.5) exposure has been extensively linked to reproductive and developmental dysfunctions, yet the underlying mechanisms remain elusive. This study employed single-cell RNA sequencing (scRNA-seq) to investigate PM2.5-induced changes in uterine cell populations and gene expr...
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Elsevier
2024-10-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324010443 |
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| author | Shuyin Duan Yongfei Zheng Jiaqi Tian Lin Zhang |
| author_facet | Shuyin Duan Yongfei Zheng Jiaqi Tian Lin Zhang |
| author_sort | Shuyin Duan |
| collection | DOAJ |
| description | Fine particulate matter (PM2.5) exposure has been extensively linked to reproductive and developmental dysfunctions, yet the underlying mechanisms remain elusive. This study employed single-cell RNA sequencing (scRNA-seq) to investigate PM2.5-induced changes in uterine cell populations and gene expression profiles in mice during estrus and early pregnancy. Methodologically, we intranasally inoculated mice with 20 μL of 4.0 mg/mL PM2.5 suspension during their estrus and early pregnancy periods. Utilizing scRNA-seq analysis, we revealed significant alterations in cell type composition following PM2.5 exposure. Notably, we observed a marked decrease in the proportion of natural killer (NK) cells in PM2.5-exposed mice (2.00 % vs. 8.97 % in controls). Further functional enrichment analysis identified suppression of the IL-17 signaling pathway in NK cells as a key mechanism of PM2.5-induced toxicity. GSEA analysis showed in-depth details of the downregulated genes in this pathway, including Fosb, S100a8, Tnfaip3, IL-17a, and S100a9. PM2.5 exposure also disrupted intercellular communication within the uterine microenvironment, with the number of cell interactions decreasing from 483 to 315 and interaction strength reducing from 12.43 to 6.78 compared to controls. Histological examination revealed that PM2.5 exposure led to thinning of the endometrium and less prominent main branches in uterine tissues, and immunofluorescence assays corroborated the altered expression of IL-17 pathway components, showing enhanced Hsp90ab1 expression and reduced FOSB, S100A8, and S100A9 expression in PM2.5-exposed uterine tissues. These findings provide novel insights into the cellular mechanisms of PM2.5-induced reproductive toxicity, highlighting the IL-17 signaling pathway in uterine NK cells as a potential target for therapeutic interventions. Our results underscore the need for air quality regulations and open new avenues for developing biomarkers and targeted therapies to mitigate the reproductive risks associated with PM2.5 exposure. |
| format | Article |
| id | doaj-art-34eeed8d55f440788d5d0ef526f3db35 |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-34eeed8d55f440788d5d0ef526f3db352025-08-20T01:54:44ZengElsevierEcotoxicology and Environmental Safety0147-65132024-10-0128411696810.1016/j.ecoenv.2024.116968Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicityShuyin Duan0Yongfei Zheng1Jiaqi Tian2Lin Zhang3School of Public Health and Health Management, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250001, ChinaSchool of Public Health and Health Management, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250001, ChinaClinical Medical Research Center for Women and Children Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China; NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai 200032, China; Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Jinan 250001, ChinaClinical Medical Research Center for Women and Children Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China; NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai 200032, China; Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Jinan 250001, China; Corresponding author at: Clinical Medical Research Center for Women and Children Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China.Fine particulate matter (PM2.5) exposure has been extensively linked to reproductive and developmental dysfunctions, yet the underlying mechanisms remain elusive. This study employed single-cell RNA sequencing (scRNA-seq) to investigate PM2.5-induced changes in uterine cell populations and gene expression profiles in mice during estrus and early pregnancy. Methodologically, we intranasally inoculated mice with 20 μL of 4.0 mg/mL PM2.5 suspension during their estrus and early pregnancy periods. Utilizing scRNA-seq analysis, we revealed significant alterations in cell type composition following PM2.5 exposure. Notably, we observed a marked decrease in the proportion of natural killer (NK) cells in PM2.5-exposed mice (2.00 % vs. 8.97 % in controls). Further functional enrichment analysis identified suppression of the IL-17 signaling pathway in NK cells as a key mechanism of PM2.5-induced toxicity. GSEA analysis showed in-depth details of the downregulated genes in this pathway, including Fosb, S100a8, Tnfaip3, IL-17a, and S100a9. PM2.5 exposure also disrupted intercellular communication within the uterine microenvironment, with the number of cell interactions decreasing from 483 to 315 and interaction strength reducing from 12.43 to 6.78 compared to controls. Histological examination revealed that PM2.5 exposure led to thinning of the endometrium and less prominent main branches in uterine tissues, and immunofluorescence assays corroborated the altered expression of IL-17 pathway components, showing enhanced Hsp90ab1 expression and reduced FOSB, S100A8, and S100A9 expression in PM2.5-exposed uterine tissues. These findings provide novel insights into the cellular mechanisms of PM2.5-induced reproductive toxicity, highlighting the IL-17 signaling pathway in uterine NK cells as a potential target for therapeutic interventions. Our results underscore the need for air quality regulations and open new avenues for developing biomarkers and targeted therapies to mitigate the reproductive risks associated with PM2.5 exposure.http://www.sciencedirect.com/science/article/pii/S0147651324010443Fine particulate matterReproductionToxicitySingle-cell RNA sequencingNatural killer cellsIL-17 signaling pathway |
| spellingShingle | Shuyin Duan Yongfei Zheng Jiaqi Tian Lin Zhang Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicity Ecotoxicology and Environmental Safety Fine particulate matter Reproduction Toxicity Single-cell RNA sequencing Natural killer cells IL-17 signaling pathway |
| title | Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicity |
| title_full | Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicity |
| title_fullStr | Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicity |
| title_full_unstemmed | Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicity |
| title_short | Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicity |
| title_sort | single cell rna sequencing of estrual mice reveals pm2 5 induced uterine cell heterogeneity and reproductive toxicity |
| topic | Fine particulate matter Reproduction Toxicity Single-cell RNA sequencing Natural killer cells IL-17 signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324010443 |
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