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三聚氰胺通过下调小鼠睾丸中 p38 的磷酸化及其下游转录因子 Max 和 Sap1a 的表达水平诱导生殖功能障碍。

Melamine induces reproductive dysfunction via down-regulated the phosphorylation of p38 and downstream transcription factors Max and Sap1a in mice testes.

机构信息

Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China.

College of Animal Science, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China.

出版信息

Sci Total Environ. 2021 May 20;770:144727. doi: 10.1016/j.scitotenv.2020.144727. Epub 2021 Jan 22.

DOI:10.1016/j.scitotenv.2020.144727
PMID:33736362
Abstract

Melamine poisoning incidents and potential health risks raise global attention. Recent studies imply that melamine exposure is related to male reproductive dysfunction, however, the underlying mechanisms are unclear. In this study, 32 male Kunming mice were administered with 0, 12.5, 25, and 50 mg/L melamine via drinking water for 13 weeks, respectively. Sperm quality, testicular morphology, and the mRNA expression levels of MAPK family members p38, ERK5, ERK1/2, JNK1/2/3 and their downstream transcription factors GADD153, MAX, MEF2C, CREB, c-Myc, JunD, c-JUN, Sap1a, p53, ATF-2, Elk1, and Nur77 in testes were investigated. The results revealed that low-dose melamine exposure reduced sperm quality, altered the testicular histological structure, and reduced the mRNA expression levels of p38, ERK1/2, MAX and Sap1a in the testes. The p38 and phosphorylated-p38 expressions analysis further suggested that the down-regulated phosphorylation of p38 and downstream transcription factors MAX and Sap1a play key roles in male reproductive dysfunction caused by melamine. Altogether, our study provides a new insight to elucidate the underlying mechanisms by which melamine induces male reproductive toxicity, and to evaluate the health risks of melamine.

摘要

三聚氰胺中毒事件和潜在的健康风险引起了全球关注。最近的研究表明,三聚氰胺暴露与男性生殖功能障碍有关,但潜在的机制尚不清楚。在这项研究中,32 只雄性昆明小鼠分别通过饮用水给予 0、12.5、25 和 50mg/L 三聚氰胺,为期 13 周。研究了精子质量、睾丸形态以及 MAPK 家族成员 p38、ERK5、ERK1/2、JNK1/2/3 及其下游转录因子 GADD153、MAX、MEF2C、CREB、c-Myc、JunD、c-JUN、Sap1a、p53、ATF-2、Elk1 和 Nur77 在睾丸中的 mRNA 表达水平。结果表明,低剂量三聚氰胺暴露降低了精子质量,改变了睾丸组织学结构,并降低了睾丸中 p38、ERK1/2、MAX 和 Sap1a 的 mRNA 表达水平。p38 和磷酸化-p38 的表达分析进一步表明,p38 及其下游转录因子 MAX 和 Sap1a 的磷酸化下调在三聚氰胺引起的男性生殖功能障碍中起关键作用。总之,我们的研究为阐明三聚氰胺诱导男性生殖毒性的潜在机制以及评估三聚氰胺的健康风险提供了新的见解。

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