title: Deoxynivalenol exposure induces autophagy/apoptosis and epigenetic modification changes during porcine oocyte maturation.
abstract: Deoxynivalenol (DON) is a widespread trichothecene mycotoxin which contaminates agricultural staples and elicits a complex spectrum of toxic effects on humans and animals. It has been shown that DON impairs oocyte maturation, reproductive function and causes abnormal fetal development in mammals; however, the mechanisms remain unclear. In the present study, we investigate the possible reasons of the toxic effects of DON on porcine oocytes. Our results showed that DON significantly inhibited porcine oocyte maturation and disrupted meiotic spindle by reducing p-MAPK protein level, which caused retardation of cell cycle progression. In addition, up-regulated LC3 protein expression and aberrant Lamp2, LC3 and mTOR mRNA levels were observed with DON exposure, together with Annexin V-FITC staining assay analysis, these results indicated that DON treatment induced autophagy/apoptosis in porcine oocytes. We also showed that DON exposure increased DNA methylation level in porcine oocytes through altering DNMT3A mRNA levels. Histone methylation levels were also changed showing with increased H3K27me3 and H3K4me2 protein levels, and mRNA levels of their relative methyltransferase genes, indicating that epigenetic modifications were affected. Taken together, our results suggested that DON exposure reduced porcine oocytes maturation capability through affecting cytoskeletal dynamics, cell cycle, autophagy/apoptosis and epigenetic modifications.
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.
authors.forename: Qiao-Chu
authors.initials: QC
authors.lastname: Wang
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: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Animal Science, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Xiang-Shun
authors.initials: XS
authors.lastname: Cui
authors.affiliation: Department of Animal Science, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Nam-Hyung
authors.initials: NH
authors.lastname: Kim
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: sunsc@njau.edu.cn.
authors.forename: Shao-Chen
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002453:Cell Cycle; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic; D005260:Female; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects*; D013552:Swine; D014255:Trichothecenes / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D008869:Microtubule-Associated Proteins; D014255:Trichothecenes; D020928:Mitogen-Activated Protein Kinases; C007262:deoxynivalenol
keywords: Autophagy; Cell cycle; Deoxynivalenol; Epigenetic modifications; Porcine oocyte