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2,3',4,4',5-五氯联苯通过 AhR/Cyp1a1 诱导小鼠生殖细胞中线粒体依赖性凋亡。

2,3',4,4',5-Pentachlorobiphenyl induces mitochondria-dependent apoptosis mediated by AhR/Cyp1a1 in mouse germ cells.

机构信息

Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan 250014, China; Dongying Institute, Shandong Normal University, Dongying 257000, China.

Department of Toxicology, Shandong Center for Disease Control and Prevention, Jinan 250014, China.

出版信息

J Hazard Mater. 2023 Mar 5;445:130547. doi: 10.1016/j.jhazmat.2022.130547. Epub 2022 Dec 5.

Abstract

Polychlorinated biphenyls (PCBs) are environmental organic pollutants widely used in industry that can bioaccumulate and affect the reproductive systems of male animals of different species. 2,3',4,4',5-Pentachlorobiphenyl (PCB118) is a representative of the 209 toxic PCB congeners. In this study, male mice were exposed to PCB118 at 0, 50, and 500 μg/kg/day for 35 days beginning 3-4 weeks after birth. The results of the study showed that PCB118 exposure during puberty reduced testicular quality, caused tissue damage, decreased sperm motility and sperm count, and increased malformation and testicular cell apoptosis in mice. Moreover, PCB118 increased the oxidative stress levels in sperm and testicular tissue and the expression of aryl hydrocarbon receptor (AhR) and Cyp1a1 and siginificantly decreased the level of nuclear factor-erythroid 2-related factor 2 (Nrf2). The results indicate that PCB118 can activate the AhR/Cyp1a1 pathway and inhibit Nrf2 expression to aggravate testicular oxidative stress and induce cell apoptosis, resulting in testicular and sperm quality damage.

摘要

多氯联苯(PCBs)是一种广泛应用于工业的环境有机污染物,能够在生物体内积累,并影响不同物种雄性动物的生殖系统。2,3',4,4',5-五氯联苯(PCB118)是 209 种有毒多氯联苯同系物的代表之一。在这项研究中,雄性小鼠从出生后 3-4 周开始,每天接受 0、50 和 500μg/kg 的 PCB118 暴露,持续 35 天。研究结果表明,青春期接触 PCB118 会降低睾丸质量,导致组织损伤,降低精子活力和数量,并增加小鼠的畸形和睾丸细胞凋亡。此外,PCB118 增加了精子和睾丸组织中的氧化应激水平,以及芳香烃受体(AhR)和 Cyp1a1 的表达,并显著降低了核因子-红细胞 2 相关因子 2(Nrf2)的水平。这些结果表明,PCB118 可以激活 AhR/Cyp1a1 途径,抑制 Nrf2 的表达,加重睾丸氧化应激并诱导细胞凋亡,从而导致睾丸和精子质量受损。

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