title: Toxic effects of HT-2 toxin on mouse oocytes and its possible mechanisms.
abstract: T-2 toxin is one of the type A trichothecene mycotoxins that is considered to be the most toxic of the trichothecenes. T-2 toxin has been shown to exert various toxic effects in farm animals and humans, as it induces lesions in the brain and in lymphoid, hematopoietic, and gastrointestinal tissues. HT-2 toxin is the major metabolite of T-2 toxin. There is little information regarding the effects of HT-2 toxin on the female reproductive system, particularly oocyte maturation. Thus, in this study, we investigated the toxic effects of HT-2 on mouse oocyte maturation and its possible mechanisms of action. HT-2 toxin exposure disrupted oocyte maturation, reduced actin expression in both the oocyte cortex and cytoplasm, and disrupted meiotic spindle morphology by reducing p-MAPK protein level. HT-2 toxin exposure also induced oxidative stress and resulted in oocyte apoptosis, as shown by ROS accumulation, increased SOD mRNA level, and the expression of the early apoptosis marker Annexin V and increased caspase-3 and bax mRNA levels. Additionally, HT-2 toxin exposure increased LC3 and ATG12 protein levels and lc3 and atg14 mRNA levels, which indicated that HT-2 toxin induced autophagy in mouse oocytes. We also examined for possible epigenetic modifications. Fluorescence intensity analysis showed that 5mC level increased after HT-2 toxin exposure, whereas H3K9me2 and H3K27me3 levels decreased after HT-2 toxin exposure, which indicated that DNA and histone methylations were altered. Thus, our results indicated that HT-2 toxin exposure reduced mouse oocyte maturation capability by affecting cytoskeletal dynamics, apoptosis/autophagy, oxidative stress, and epigenetic modifications.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Zhu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Duan
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China. sunsc@njau.edu.cn.
authors.forename: Shao-Chen
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013605:T-2 Toxin / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000199:Actins; D013605:T-2 Toxin; C012351:HT-2 toxin
keywords: Apoptosis and autophagy; Cytoskeleton; Epigenetic modifications; HT-2 toxin; Oocyte; Oxidative stress