Back to Search Start Over

BDE-209 induced spermatogenesis disorder by inhibiting SETD8/H4K20me1 related histone methylation in mice.

Authors :
Li X
Zhang Y
Gao L
Yang X
Zhou G
Sang Y
Xue J
Shi Z
Sun Z
Zhou X
Source :
The Science of the total environment [Sci Total Environ] 2023 Mar 15; Vol. 864, pp. 161162. Date of Electronic Publication: 2022 Dec 23.
Publication Year :
2023

Abstract

Past studies have observed that decabromodiphenyl ether (BDE-209) induces reproductive and developmental toxicity, but the specific mechanism remains unclear. Based on our previous work, male mice were orally given BDE-209 at 75 mg/kg/d via continuous exposure for one spermatozoon development period (50 days) and then stopping exposure for another 50 days. The mouse spermatocyte line GC-2spd was used to examine the toxic effects of BDE-209 on histone methylation and spermatogenesis. The findings indicated that BDE-209 damaged testis and epididymis structure, induced spermatogenic cell apoptosis, and decreased sperm quantity and quality after the 50-day exposure. Furthermore, BDE-209 lowered the levels of SETD8/H4K20me1 and activated the upstream signaling of DNA damage response (Mre11/Rad50/NBS1), thereby causing spermatogenic cell cycle arrest and apoptosis. Downregulation of meiotic promoter Stra8 was associated with a decrease in SETD8 after BDE-209 exposure. After stopping the exposure for 50 days, reproductive system damage and meiosis and cell cycle inhibition due to histone methylation did not improve. In vitro experiments revealed that Setd8 overexpression upregulated the histone methylation and Stra8 expression but did not promote the cell cycle in GC-2 cells. Therefore, BDE-209 exposure impaired spermatogenesis by affecting SETD8/H4K20me1-linked histone methylation and inhibiting meiosis initiation and cell cycle progression, thereby resulting in long-term male reproductive toxicity.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2022 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1879-1026
Volume :
864
Database :
MEDLINE
Journal :
The Science of the total environment
Publication Type :
Academic Journal
Accession number :
36572290
Full Text :
https://doi.org/10.1016/j.scitotenv.2022.161162