Zearalenone perturbs the circadian clock and inhibits testosterone synthesis in mouse Leydig cells
Zearalenone perturbs the circadian clock and inhibits testosterone synthesis in mouse Leydig cells
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玉米赤霉烯酮扰乱生物钟并抑制小鼠睾丸间质细胞的睾酮合成
DOI：
10.1080/15287394.2020.1841699
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Huatao Chen
中科院分区：
文献类型：
--
作者：
Lijia Zhao;Yaoyao Xiao;Cuimei Li;Jing Zhang;Yaojia Zhang;Meina Wu;Tiantian Ma;Huatao Chen;Xiaoyu Wang;Haizhen Jiang;Qian Li;Hongcong Zhao;Yiqun Wang;Aihua Wang;Yaping Jin;Huatao Chen
玉米赤霉烯酮（ZEA）是一种真菌毒素，通过干扰睾丸间质细胞（LC）合成和分泌睾酮来损害生殖能力，但其机制尚不清楚。在LCs中鉴定了生物钟和类固醇基因的稳健节律性。本研究的目的是检查ZEA是否显着减弱小鼠睾丸Leydig细胞系（TM 3）中核心时钟基因（Bmal 1、Dbp、Per2和Nr 1d 1）以及类固醇生成基因（星星、Hsd3b2和Cyp 11 a1）的转录。Western印迹证实BMAL1、NR1D1和星星蛋白水平下降。ZEA还抑制分泌的睾酮水平。在从小鼠PER 2：：LUCIFERASE报告基因敲除中分离的原代LC中，ZEA降低了PER 2：：LUC表达的幅度，并诱导了相移和周期延长。在原发性LC中，ZEA还抑制了核心时钟和类固醇生成基因的表达水平，降低了BMAL1的蛋白水平，并减少了睾酮分泌。暴露于ZEA 1周的小鼠睾丸中核心时钟和类固醇生成基因的体内表达降低，导致血清睾酮水平降低。总之，数据表明，ZEA可能通过减弱LC中的昼夜节律钟而损害睾酮合成，最终导致雄性哺乳动物的生殖功能障碍。
Zearalenone (ZEA), a mycotoxin, is known to impair reproductive capability by disrupting the synthesis and secretion of testosterone by Leydig cells (LCs), although the mechanism is unknown. Robust rhythmicity of circadian clock and steroidogenic genes were identified in LCs. The aim of this study was to examine whether ZEA significantly attenuated the transcription of core clock genes (Bmal1, Dbp, Per2, and Nr1d1) as well as steroidogenic genes (StAR, Hsd3b2, and Cyp11a1) in mouse testis Leydig cell line (TM3). Western blotting confirmed declines in BMAL1, NR1D1, and StAR protein levels. ZEA also suppressed secreted testosterone levels. In primary LCs, isolated from PER2::LUCIFERASE reporter gene knock in mice, ZEA diminished the amplitude of PER2::LUC expression, and induced a phase shift and period extension. In primary LCs, ZEA also suppressed the expression levels of core clock and steroidogenic genes, reduced protein levels of BMAL1, and decreased testosterone secretion. In vivo expression of core clock and steroidogenic genes were reduced in testes of mice exposed to ZEA for 1 week leading to decreased serum testosterone levels. In summary, data suggest that ZEA may impair testosterone synthesis through attenuation of the circadian clock in LCs culminating in reproductive dysfunction in male mammals .
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影响因子：
3.5
作者：
Alvarez, J. D.;Hansen, Amanda;Sehgal, Amita
通讯作者：
Sehgal, Amita
DOI：
--
发表时间：
2002
期刊：
--
影响因子：
--
作者：
S. Tischkau;Jennifer W Mitchell;S. Tyan;G. F. Buchanan;M. Gillette
通讯作者：
S. Tischkau;Jennifer W Mitchell;S. Tyan;G. F. Buchanan;M. Gillette
DOI：
10.1016/j.bbrc.2012.02.164
发表时间：
2012-04-06
影响因子：
3.1
作者：
Chen, Huatao;Chu, Guiyan;Hattori, Masa-aki
通讯作者：
Hattori, Masa-aki
影响因子：
5.3
作者：
Ikeda, Masayuki;Ikeda, Masaaki
通讯作者：
Ikeda, Masaaki
影响因子：
0.7
作者：
E. Skurikhin;A. Pakhomova;O. Pershina;V. A. Krupin;N. N. Ermakova-N.;E. Pan;A. I. Kudryashova;L. A. Ermolaeva;E. S. Khmelevskaya;V. E. Goldberg;V. Zhdanov;A. Dygai
通讯作者：
E. Skurikhin;A. Pakhomova;O. Pershina;V. A. Krupin;N. N. Ermakova-N.;E. Pan;A. I. Kudryashova;L. A. Ermolaeva;E. S. Khmelevskaya;V. E. Goldberg;V. Zhdanov;A. Dygai