Department of Obstetrics and Gynecology, Taoyuan General Hospital, Ministry of Health & Welfare, Taoyuan City, Taiwan.
Rehabilitation and Technical Aid Center, Taipei Veterans General Hospital, Taipei City, Taiwan.
Drug Chem Toxicol. 2022 Jul;45(4):1449-1460. doi: 10.1080/01480545.2020.1838537. Epub 2020 Oct 27.
The current study has focused on the effects of enniatin B (ENN B, a major mycotoxin produced by fungi) on early embryonic development. In analysis, mouse blastocysts were incubated in medium with ENN B (0-40 μM) or 0.5% DMSO (control group) for 24 hours. In an animal study, blastocysts were collected from mice which were intravenously injected with ENN B (1, 3, 5, and 7mg/kg body weight/day) for 4 days in order to analyze apoptosis and necrosis via Annexin V/PI staining assay; and proliferation using dual differential staining. Exposure to low ENN B concentration (10 μM and 3 mg/kg/day ) promoted Reactive Oxygen Species (ROS) generation and apoptosis in the Inner Cell Mass (ICM), the mass of cells inside the blastocyst, impairing post-implantation development alone. On the other hand, exposure to a higher ENN B concentration (40 μM and 7 mg/kg/day ) induced ROS generation and decreased in intracellular ATP which encouraged necrotic processes in both trophectoderm (TE) and ICM of blastocysts leading to impaired implantation and post-implantation development. Moreover, 5 and 7 mg/kg/day ENN B intraperitoneal injection to female mice for 4 days has caused downregulation of and expressions and increased ROS generation in the liver of newborn mice. Over all, ENN B can induce apoptosis and/or necrosis depending on the treatment dosage in mouse blastocysts. ENN B-induced necrosis in blastocysts may exert long-term harmful effects on next-generation newborns.
本研究主要关注了真菌产生的主要霉菌毒素——恩镰孢菌素 B(ENN B)对早期胚胎发育的影响。在分析中,将小鼠囊胚在含有 ENN B(0-40 μM)或 0.5% DMSO(对照组)的培养基中孵育 24 小时。在一项动物研究中,从连续 4 天静脉注射 ENN B(1、3、5 和 7mg/kg 体重/天)的小鼠中收集囊胚,通过 Annexin V/PI 染色分析来检测凋亡和坏死;并通过双重差异染色检测增殖情况。低浓度的 ENN B(10 μM 和 3 mg/kg/天)暴露会促进内细胞团(ICM)中活性氧物质(ROS)的产生和凋亡,损害胚胎着床后的发育。另一方面,高浓度的 ENN B(40 μM 和 7 mg/kg/天)暴露会诱导 ROS 的产生和细胞内 ATP 的减少,从而促进囊胚滋养外胚层(TE)和 ICM 中的坏死过程,导致着床和胚胎着床后发育受损。此外,连续 4 天向雌性小鼠腹腔注射 5 和 7mg/kg/天的 ENN B 会导致新生小鼠肝脏中 和 的表达下调以及 ROS 的产生增加。总之,ENN B 可以根据在小鼠囊胚中的处理剂量诱导凋亡和/或坏死。ENN B 诱导的囊胚坏死可能会对下一代新生儿产生长期的有害影响。