Characterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing

Zhang, Wei1,2; Xia, Siyu1,2; Zhong, Xiaoru1; Gao, Guoyong3; Yang, Jing1; Wang, Shuang1; Cao, Min1; Liang, Zhen1; Yang, Chuanbin1; Wang, Jigang1,4,5,6

2022-07-22

10.1093/pcmedi/pbac016

Precision Clinical Medicine   影响因子和分区

2096-5303

2516-1571

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 76 859 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.

single-cell RNA-sequencing spermatogenesis BDE47 reproductive toxicity

ESCI

英语

第一 ; 通讯

National Natural Science Foundation of China[82003721] ; Shenzhen Science and Technology Innovation Commission["JCYJ20210324114014039","JCYJ20210324115800001"] ; China Postdoctoral Science Foundation[2020M683182] ; Guangdong Basic and Applied Basic Research Foundation[2020A1515110549] ; National Key Research and Development Program of China[2020YFA0908000] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; Sanming Project of Medicine in Shenzhen[SZSM201612034]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000828813400001

OXFORD UNIV PRESS

Web of Science

1.Southern Univ Sci & Technol, Affiliated Hosp 1, Jinan Univ,Dept Geriatr, Clin Med Coll 2,Shenzhen Peoples Hosp, Shenzhen 518020, Peoples R China
2.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou 510632, Peoples R China
3.Southern Univ Sci & Technol, Affiliated Hosp 1, Jinan Univ,Dept Spine Surg, Clin Med Coll 2,Shenzhen Peoples Hosp, Shenzhen 518020, Peoples R China
4.China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China
5.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
6.Southern Med Univ, Dongguan Maternal & Child Hlth Care Hosp, Ctr Reprod Med, Dongguan 523125, Peoples R China

Zhang, Wei,Xia, Siyu,Zhong, Xiaoru,et al. Characterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing[J]. Precision Clinical Medicine,2022,5(3).

Zhang, Wei.,Xia, Siyu.,Zhong, Xiaoru.,Gao, Guoyong.,Yang, Jing.,...&Wang, Jigang.(2022).Characterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing.Precision Clinical Medicine,5(3).

Zhang, Wei,et al."Characterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing".Precision Clinical Medicine 5.3(2022).