不孕妇女脂肪分布差异与辅助生殖结果的关联:一项前瞻性队列研究

Role of sleep in asthenospermia induced by di (2-ethyl-hexyl) phthalate

睡眠在邻苯二甲酸二(2-乙基-己基)诱导的弱精子症中的作用

Authors：Li XL, Cai XY, Ning X, Liang YY, Hong Y, Li QM, Hu D, Zheng YZ, Cai Y, Xu T, Zhao LL.

Source：Environ Sci Pollut Res Int.  

DOI：10.1007/s11356-024-32030-9

Abstract

Di (2-ethyl-hexyl) phthalate (DEHP) mainly enters the human body through the digestive tract, respiratory tract, and skin. At the same time, it has reproductive and developmental toxicity, neurotoxicity, and so on, which can cause the decrease of sperm motility. Asthenospermia is also known as low sperm motility, and the semen quality of men in some areas of China is declining year by year. Interestingly, previous studies have shown that sleep disorders can also lead to asthenospermia. However, the relationship between sleep, DEHP, and asthenospermia is still unclear. Analysis of the National Health and Nutrition Examination Survey (NHANES) population database showed that DEHP was associated with sleep disorders, and subsequent experiments in mice and Drosophila indicated that DEHP exposure had certain effects on sleep and asthenospermia. Furthermore, we analyzed the Comparative Toxicogenomics Database (CTD) to find out the common signaling pathway among the three: hypoxia-inducible factor 1(HIF-1). Then Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to screen out the proteins that DEHP affected the HIF-1 pathway: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), serine/threonine-protein kinase (AKT1), epidermal growth factor receptor (EGFR), and finally Western blot analysis was used to detect the expression levels of the three proteins. Compared with the control group, DEHP decreased the protein expression levels of GAPDH and AKT1 in the HIF-1 pathway, and caused sleep disorders and decreased sperm motility. This study provides preliminary evidence for exploring the mechanism among DEHP, sleep disorders, and asthenospermia.

摘要

邻苯二甲酸二(2-乙基己基)酯(DEHP)主要通过消化道、呼吸道和皮肤进入人体。同时，它具有生殖和发育毒性、神经毒性等，可引起精子活力下降。弱精子症也被称为精子活力低，中国一些地区男性的精液质量正在逐年下降。有趣的是，之前的研究表明睡眠障碍也会导致弱精子症。然而，睡眠、DEHP和弱精子症之间的关系尚不清楚。对美国国家健康与营养调查(NHANES)人口数据库的分析显示，DEHP与睡眠障碍有关，随后在小鼠和果蝇身上进行的实验表明，DEHP暴露对睡眠和弱精子症有一定影响。此外，我们分析了比较毒物基因组学数据库(CTD)，找出了三者之间的共同信号通路:缺氧诱导因子1(HIF-1)。然后利用相互作用基因/蛋白检索工具(STRING)筛选DEHP影响HIF-1通路的蛋白:甘油醛-3-磷酸脱氢酶(GAPDH)、丝氨酸/苏氨酸蛋白激酶(AKT1)、表皮生长因子受体(EGFR)，最后采用Western blot分析检测这三种蛋白的表达水平。与对照组相比，DEHP降低了HIF-1通路中GAPDH和AKT1的蛋白表达水平，导致睡眠障碍和精子活力下降。本研究为探讨DEHP与睡眠障碍、弱精子症的发病机制提供了初步依据。