biostudies-literatureUnknown5(3)Zhang W<h4>Background</h4>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.<h4>Methods</h4>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 76 859 cells.<h4>Results</h4>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 <i>Kdm5b</i> (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.<h4>Conclusions</h4>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.Precision clinical medicinepbac016https://www.ebi.ac.uk/biostudies/studies/S-EPMC9306015biostudies-literatureCharacterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing.PMC9306015Zhang WYang JCao MWang SLiang ZXia SZhong XGao GYang CWang JfalseCharacterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing.<h4>Background</h4>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.<h4>Methods</h4>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 76 859 cells.<h4>Results</h4>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 <i>Kdm5b</i> (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.<h4>Conclusions</h4>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.2022-01-01T00:00:00Z2022 Sep2024-11-06T19:08:43.881Z2024-11-06T19:08:43.881ZS-EPMC93060153587560410.1093/pcmedi/pbac016