Abstract
The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.
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Data availability
The datasets used during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
I express my gratitude to all who helped me during the writing of this thesis. I gratefully acknowledge the help of my supervisor, Mr. Wsd, who has offered me valuable suggestions in my academic studies. Without his consistent and illuminating instruction, this thesis could not have reached its present form.
I am also grateful to Wjk. Under his patient guidance, I learned and completed a substantial amount of work. I am also deeply indebted to Cjd for his help.
I am indebted to my family for their continuous support and encouragement.
I thank AJE for polishing this article.
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This study was supported by the National Natural Science Foundation of China (Grant number 82071632); the Innovation Program for Chongqing’s Overseas Returnees (Grant number cx 2019030); the Chongqing Municipal Health Commission (High-level Medical Reserved Personnel Training Project of Chongqing); and the Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515110796).
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Kl designed the whole experiment, built the model, detected the results, summarized the data, and wrote the first draft. Cjd participated in the modeling. Wjl proposed constructive suggestions for the modification of the paper. Ztx proposed the idea for the experiment. Wyx and Wyh verified the experimental design. Hld prepared the experimental reagent materials. Zxq participated in the data processing. The visualization of the experimental results was guided by Lcl. Slj supervised the experiment, and Wgh reviewed the article and agreed to contribute. Wsd manages and supports the whole project.
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Kang, L., Chen, J., Wang, J. et al. Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused by DEHP exposure. Environ Sci Pollut Res 29, 13478–13490 (2022). https://doi.org/10.1007/s11356-021-16701-5
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DOI: https://doi.org/10.1007/s11356-021-16701-5