Xia Ling-Zi, Yue Jun-Zhe, Wu Li-Jun, Jin Qian-Ying, Yang Yi-Pei, Yu Jing-Yang, Pan Rui-Zhe, Zhang Xin, Wu Xiao-Ying, Zhu Jiayin, Gao Hai-Tao
Department of Environmental Hygiene and Toxicology, School of Public Health, Wenzhou Medical University, Wenzhou 325035, China.
Department of Environmental Hygiene and Toxicology, School of Public Health, Wenzhou Medical University, Wenzhou 325035, China; Qidong Center for Disease Control and Prevention, Qidong 226200, China.
Toxicol Appl Pharmacol. 2025 Nov;504:117544. doi: 10.1016/j.taap.2025.117544. Epub 2025 Sep 4.
Phthalates (PEs) are widespread in environment, and human beings are unavoidably exposing to the mixture of PEs, which may induce male reproductive health risks. In order to investigate the mechanism of male reproductive injuries caused by the mixture of di-2-ethylhexyl phthalate, dibutyl phthalate and butyl benzyl phthalate (MPEs), male rats were orally exposed to 16 mg/kg/d MPEs (L-MPEs) and 450 mg/kg/d MPEs (H-MPEs) for 90 days, and the results showed that MPEs decreased the weights of testes, epididymis and periepididymis fat, decreased serum levels of male hormones, increased abnormal sperm rate, and caused testicular histopathological damages, such as atrophy and cavitation of seminiferous tubules, spermatids exfoliation, Leydig cells hyperplasia and accumulation of lipid droplets in the testicular interstitium. Testicular transcriptomic analysis identified 100 differently expressed genes (DEGs) in L-MPEs group and 10,880 DEGs in H-MPEs group, and these DEGs mainly involved in signaling pathways of focal adhesion, PI3K-Akt, AGE-RAGE, axon guidance, PPAR, MAPK and etc. Testicular Paxillin and vinculin were significantly upregulated in MPEs treated groups, initially verified that focal adhesion was a pathway of male reproductive injuries induced by MPEs. This study provides new ideas for the further researches on the mechanism of MPEs' male reproductive toxicity.
邻苯二甲酸酯（PEs）在环境中广泛存在，人类不可避免地会接触到多种PEs的混合物，这可能会引发男性生殖健康风险。为了探究邻苯二甲酸二（2-乙基己基）酯、邻苯二甲酸二丁酯和邻苯二甲酸丁苄酯混合物（MPEs）导致男性生殖损伤的机制，将雄性大鼠分别以16毫克/千克/天的MPEs（低剂量MPEs，L-MPEs）和450毫克/千克/天的MPEs（高剂量MPEs，H-MPEs）进行90天的灌胃暴露实验。结果显示，MPEs降低了睾丸、附睾和附睾周围脂肪的重量，降低了血清中雄性激素水平，增加了精子畸形率，并导致睾丸组织病理学损伤，如曲细精管萎缩和空泡化、精子细胞脱落、睾丸间质细胞增生以及脂滴积聚。睾丸转录组分析在L-MPEs组中鉴定出100个差异表达基因（DEGs），在H-MPEs组中鉴定出10880个DEGs，这些DEGs主要涉及粘着斑、PI3K-Akt、AGE-RAGE、轴突导向、PPAR、MAPK等信号通路。睾丸中的桩蛋白和纽蛋白在MPEs处理组中显著上调，初步证实粘着斑是MPEs诱导男性生殖损伤的一条途径。本研究为进一步深入研究MPEs的男性生殖毒性机制提供了新思路。
