Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Sciences and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China.
Toxins (Basel). 2024 Feb 1;16(2):73. doi: 10.3390/toxins16020073.
Zearalenone (ZEN), a non-steroidal with an estrogen effect, can cause damage to the gastrointestinal tract, immune organs, liver, and reproductive system. Further analysis of the mechanism of ZEN has become an important scientific issue. We have established in vivo and in vitro models of ZEN intervention, used AMPK/mTOR as a targeted pathway for ZEN reproductive toxicity, and explored the molecular mechanism by which ZEN may induce uterine hypertrophy in weaned piglets. Our study strongly suggested that ZEN can activate the phosphorylation of AMPK in uterine endometrial epithelium cells, affect the phosphorylation level of mTOR through TSC2 and Rheb, induce autophagy, upregulate the expression of proliferative genes PCNA and BCL2, downregulate the expression of apoptotic gene BAX, promote uterine endometrial epithelium cells proliferation, and ultimately lead to thickening of the endometrial and myometrium, increased density of uterine glands, and induce uterine hypertrophy.
玉米赤霉烯酮（ZEN）是一种具有雌激素效应的非甾体化合物，可对胃肠道、免疫器官、肝脏和生殖系统造成损伤。进一步分析 ZEN 的作用机制已成为一个重要的科学问题。我们建立了 ZEN 干预的体内和体外模型，以 AMPK/mTOR 作为 ZEN 生殖毒性的靶向途径，探讨了 ZEN 可能引起断奶仔猪子宫肥大的分子机制。我们的研究强烈表明，ZEN 可激活子宫子宫内膜上皮细胞中 AMPK 的磷酸化，通过 TSC2 和 Rheb 影响 mTOR 的磷酸化水平，诱导自噬，上调增殖基因 PCNA 和 BCL2 的表达，下调凋亡基因 BAX 的表达，促进子宫子宫内膜上皮细胞增殖，最终导致子宫内膜和子宫肌层增厚、子宫腺密度增加，引起子宫肥大。
