Background:The growing male reproductive diseases have been linked to higher exposure to certain environmental compounds such as 2,2,4,4-tetrabromodiphenyl ether(BDE47)that are widely distributed in the food chain.How...Background:The growing male reproductive diseases have been linked to higher exposure to certain environmental compounds such as 2,2,4,4-tetrabromodiphenyl ether(BDE47)that are widely distributed in the food chain.However,the specific underlying molecular mechanisms for BDE47-induced male reproductive toxicity are not completely understood.Methods:Here,for the first time,advanced single-cell RNA sequencing(ScRNA-seq)was employed to dissect BDE47-induced prepubertal testicular toxicity in mice from a pool of 76859 cells.Results:Our ScRNA-seq results revealed shared and heterogeneous information of differentially expressed genes,signaling pathways,transcription factors,and ligands-receptors in major testicular cell types in mice upon BDE47 treatment.Apart from disruption of hormone homeostasis,BDE47 was discovered to downregulate multiple previously unappreciated pathways such as double-strand break repair and cytokinesis pathways,indicative of their potential roles involved in BDE47-induced testicular injury.Interestingly,transcription factors analysis of ScRNA-seq results revealed that Kdm5b(lysine-specific demethylase 5B),a key transcription factor required for spermatogenesis,was downregulated in all germ cells as well as in Sertoli and telocyte cells in BDE47-treated testes of mice,suggesting its contribution to BDE47-induced impairment of spermatogenesis.Conclusions:Overall,for the first time,we established the molecular cell atlas of mice testes to define BDE47-induced prepubertal testicular toxicity using the ScRNA-seq approach,providing novel insight into our understanding of the underlying mechanisms and pathways involved in BDE47-associated testicular injury at a single-cell resolution.Our results can serve as an important resource to further dissect the potential roles of BDE47,and other relevant endocrine-disrupting chemicals,in inducing male reproductive toxicity.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82003721)Shenzhen Science and Technology Innovation Commission(Grants No.JCYJ20210324114014039 and JCYJ20210324115800001)+4 种基金China Postdoctoral Science Foundation(Grant No.2020M683182)Guangdong Basic and Applied Basic Research Foundation(Grant No.2020A1515110549)the National Key Research and Development Program of China(Grant No.2020YFA0908000)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.ZYYCXTD-C-202002)the Sanming Project of Medicine in Shenzhen(Grant No.SZSM201612034).
文摘Background:The growing male reproductive diseases have been linked to higher exposure to certain environmental compounds such as 2,2,4,4-tetrabromodiphenyl ether(BDE47)that are widely distributed in the food chain.However,the specific underlying molecular mechanisms for BDE47-induced male reproductive toxicity are not completely understood.Methods:Here,for the first time,advanced single-cell RNA sequencing(ScRNA-seq)was employed to dissect BDE47-induced prepubertal testicular toxicity in mice from a pool of 76859 cells.Results:Our ScRNA-seq results revealed shared and heterogeneous information of differentially expressed genes,signaling pathways,transcription factors,and ligands-receptors in major testicular cell types in mice upon BDE47 treatment.Apart from disruption of hormone homeostasis,BDE47 was discovered to downregulate multiple previously unappreciated pathways such as double-strand break repair and cytokinesis pathways,indicative of their potential roles involved in BDE47-induced testicular injury.Interestingly,transcription factors analysis of ScRNA-seq results revealed that Kdm5b(lysine-specific demethylase 5B),a key transcription factor required for spermatogenesis,was downregulated in all germ cells as well as in Sertoli and telocyte cells in BDE47-treated testes of mice,suggesting its contribution to BDE47-induced impairment of spermatogenesis.Conclusions:Overall,for the first time,we established the molecular cell atlas of mice testes to define BDE47-induced prepubertal testicular toxicity using the ScRNA-seq approach,providing novel insight into our understanding of the underlying mechanisms and pathways involved in BDE47-associated testicular injury at a single-cell resolution.Our results can serve as an important resource to further dissect the potential roles of BDE47,and other relevant endocrine-disrupting chemicals,in inducing male reproductive toxicity.
