Enniatin B induces dosage-related apoptosis or necrosis in mouse blastocysts leading to deleterious effects on embryo development.

Abstract

The current study has focused on the effects of enniatin B (ENN B, a major mycotoxin produced by Fusarium fungi) on early embryonic development. In in vitro 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 in vitro and 3 mg/kg/day in vivo) 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 in vitro and 7 mg/kg/day in vivo) 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 CXCL1, IL-1β and IL-8 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.

• Authors: Chien-Hsun Huang, Fu-Ting Wang, Wen-Hsiung Chan
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 45 Issue 4 Pg. 1449-1460 (Jul 2022) ISSN: 1525-6014 [Electronic] United States
• PMID: 33106064 (Publication Type: Journal Article)

Chemical References

• Depsipeptides
• Reactive Oxygen Species
• enniatins

Topics

• Animals
• Apoptosis
• Blastocyst (drug effects)
• Depsipeptides (toxicity)
• Embryonic Development (drug effects)
• Female
• Mice
• Necrosis (chemically induced)
• Pregnancy
• Reactive Oxygen Species (metabolism)