Yang Hong-Yuan, Luo Hui-Na, Wang Zai-Mei, Jin Dan-Dan, Yang Zeng-Ming
Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountain Region, College of Animal Science, Guizhou University, Guiyang 550025, China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Int J Mol Sci. 2025 Apr 26;26(9):4129. doi: 10.3390/ijms26094129.
Acrylamide is a class 2A carcinogen with neurotoxicity and genotoxicity. In addition to industrial production, it is ubiquitous in high-temperature heated high-carbohydrate foods. Numerous studies have confirmed the toxicity of ACR on reproduction. Implantation and decidualization are crucial processes during the establishment of pregnancy in rodents and humans. However, its effect on uterine implantation and decidualization remains poorly understood. The objective of this study is to elucidate the mechanism by which ACR affects implantation and decidualization in mice. ACR is exposed in the daily drinking water of female mice, and the dose is calculated according to the body weight of the mice. After 3 months of administration at concentrations of 0, 20, and 30 mg ACR/kg/d, female mice are mated with male mice to induce pregnancy. Compared to the control group, ACR treatment significantly reduces the number of embryo implantations and litter size. ACR treatment leads to abnormal expression of endometrial receptivity-related molecules in the luminal epithelium on day 4 of pregnancy, including a decrease in p-STAT3 level and an increase in MUC1 and MSX1 levels. The level of decidualization-related molecules is obviously downregulated by ACR. Furthermore, ACR treatment results in abnormality of oxidative stress- and ferroptosis-related protein levels at the implantation site on day 5. In conclusion, acrylamide can impair mouse implantation and decidualization by disrupting oxidative stress and ferroptosis.
丙烯酰胺是一种2A类致癌物,具有神经毒性和遗传毒性。除工业生产外,它在高温加热的高碳水化合物食品中普遍存在。大量研究已证实丙烯酰胺对生殖系统的毒性。着床和蜕膜化是啮齿动物和人类妊娠建立过程中的关键环节。然而,其对子宫着床和蜕膜化的影响仍知之甚少。本研究的目的是阐明丙烯酰胺影响小鼠着床和蜕膜化的机制。将丙烯酰胺暴露于雌性小鼠的日常饮用水中,剂量根据小鼠体重计算。以0、20和30mg丙烯酰胺/千克/天的浓度给药3个月后,将雌性小鼠与雄性小鼠交配以诱导妊娠。与对照组相比,丙烯酰胺处理显著减少了胚胎着床数和产仔数。丙烯酰胺处理导致妊娠第4天子宫腔上皮中子宫内膜容受性相关分子表达异常,包括p-STAT3水平降低以及MUC1和MSX1水平升高。蜕膜化相关分子的水平明显被丙烯酰胺下调。此外,丙烯酰胺处理导致妊娠第5天着床部位氧化应激和铁死亡相关蛋白水平异常。总之,丙烯酰胺可通过破坏氧化应激和铁死亡来损害小鼠的着床和蜕膜化。