232830The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, P. R. China.
Henan University of Chinese Medicine, Zhengzhou, P. R. China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221139444. doi: 10.1177/09603271221139444.
Di(2-ethylhexyl) phthalate (DEHP) is one of the most common organic pollutants and is added to various plastic products as a plasticizer. DEHP oxidative metabolite content in the human body is associated with DNA damage in sperm and decreased testosterone levels in blood. In this study, a DEHP-induced sperm DNA damage mouse model was replicated and improved, and the transcriptomic and proteomic characteristics of the model were observed. Male mice in the two groups were exposed to DEHP 1 g/kg/d or the same amount of normal saline for 60 days, and the sperm DNA fragmentation index (DFI) was detected by a sperm chromatin structure assay (SCSA). The mRNA and protein expression profiles of the testis were detected by RNA-seq and data-independent acquisition (DIA). The sperm DFI of the DEHP group was significantly increased. Compared with the control group, 111 differentially expressed genes (DEGs) and 2147 differentially expressed proteins (DEPs), such as Lamb2, Ahnak, Tkt, Dnah8 and Tbl2, were found in the DEHP group. These genes were mainly enriched in metabolic pathways, pathways in cancer and the PI3K-Akt signaling pathway. Our results showed that DEHP 1 g/kg/d can induce sperm DNA damage in a male mouse model after 60 days of intragastric administration. The reproductive toxicity of DEHP may be related to metabolic pathways in cancer and the PI3K-Akt signaling pathway.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是最常见的有机污染物之一，作为增塑剂添加到各种塑料制品中。人体内 DEHP 氧化代谢物的含量与精子中的 DNA 损伤和血液中睾酮水平降低有关。在本研究中，复制并改进了 DEHP 诱导的精子 DNA 损伤小鼠模型，并观察了模型的转录组和蛋白质组特征。两组雄性小鼠分别暴露于 DEHP 1g/kg/d 或等量生理盐水 60 天，通过精子染色质结构分析（SCSA）检测精子 DNA 碎片化指数（DFI）。通过 RNA-seq 和数据非依赖性采集（DIA）检测睾丸的 mRNA 和蛋白质表达谱。DEHP 组的精子 DFI 明显增加。与对照组相比，DEHP 组发现 111 个差异表达基因（DEGs）和 2147 个差异表达蛋白（DEPs），如 Lamb2、Ahnak、Tkt、Dnah8 和 Tbl2。这些基因主要富集在代谢途径、癌症途径和 PI3K-Akt 信号通路中。我们的结果表明，DEHP 1g/kg/d 经灌胃 60 天后可诱导雄性小鼠模型精子 DNA 损伤。DEHP 的生殖毒性可能与癌症途径和 PI3K-Akt 信号通路有关。
