PI3K/AKT/mTOR通路
蛋白激酶B
MAPK/ERK通路
间质细胞
化学
信号转导
信使核糖核酸
细胞生物学
生物
内科学
医学
生物化学
激素
基因
促黄体激素
作者
Aiyi Sui,Chenjuan Yao,Yanhong Chen,Yanli Li,Shali Yu,Jianhua Qu,Haiyan Wei,Juan Tang,Gang Chen
标识
DOI:10.1016/j.fct.2023.113634
摘要
Microplastics (MPs) and nanoplastics (NPs) are widely found in water, food and air, and have been found in human blood, lung and feces. Several studies in vivo have shown that MPs and NPs decrease testosterone level. However, the molecular mechanism of MPs and NPs leading to testosterone reduction remains unclear. In the present study, mice were treated with 50 μg/kg·day polystyrene (PS)-NPs by tail vein injection once daily for two consecutive days, the mRNA and protein levels of steroidogenic acute regulatory protein (StAR) decreased significantly in testis. TM3 Leydig cells were treated with non-toxic doses of PS-NPs, hypoxia-inducible factor-1α (HIF-1α) mRNA translation was induced by PS-NPs through mTOR/4E-BP1 pathway, which was activated by the ERK1/2 MAPK and AKT pathways. Simultaneously, increased HIF-1α protein inhibited StAR transcription. Additionally, reactive oxygen species production induced by PS-NPs played a central role in the activation of ERK1/2 MAPK/mTOR and AKT/mTOR signaling pathways. These results suggest that PS-NPs down-regulate StAR expression by increasing HIF-1α, which is induced by activation of mTOR/4E-BP1 through the ERK1/2 MAPK and AKT signaling pathways. Our findings provide new insight into the potential molecular mechanism by which PS-NPs impair testosterone synthesis and male reproductive function.
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