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Toxic effects of HT-2 toxin on mouse oocytes and its possible mechanisms

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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.

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References

  • Albarenque SM, Shinozuka J, Iwamoto S, Nakayama H, Doi K (1999) T-2 toxin-induced acute skin lesions in Wistar-derived hypotrichotic WBN/ILA-Ht rats. Histol Histopathol 14(2):337–342

    CAS  PubMed  Google Scholar 

  • Alm H, Greising T, Brussow KP, Torner H, Tiemann U (2002) The influence of the mycotoxins deoxynivalenol and zearalenol on in vitro maturation of pig oocytes and in vitro culture of pig zygotes. Toxicol In Vitro 16(6):643–648

    Article  CAS  PubMed  Google Scholar 

  • Chaudhari M, Jayaraj R, Bhaskar AS, Lakshmana Rao PV (2009) Oxidative stress induction by T-2 toxin causes DNA damage and triggers apoptosis via caspase pathway in human cervical cancer cells. Toxicology 262(2):153–161. doi:10.1016/j.tox.2009.06.002

    Article  CAS  PubMed  Google Scholar 

  • Desjardins AE, Hohn TM, McCormick SP (1993) Trichothecene biosynthesis in Fusarium species: chemistry, genetics, and significance. Microbiol Rev 57(3):595–604

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dugyala RR, Kim YW, Sharma RP (1994) Effects of aflatoxin B1 and T-2 toxin on the granulocyte-macrophage progenitor cells in mouse bone marrow cultures. Immunopharmacology 27(1):57–65

    Article  CAS  PubMed  Google Scholar 

  • Eppig JJ, Schroeder AC (1989) Capacity of mouse oocytes from preantral follicles to undergo embryogenesis and development to live young after growth, maturation, and fertilization in vitro. Biol Reprod 41(2):268–276

    Article  CAS  PubMed  Google Scholar 

  • Erhardt S, Su IH, Schneider R et al (2003) Consequences of the depletion of zygotic and embryonic enhancer of zeste 2 during preimplantation mouse development. Development 130(18):4235–4248

    Article  CAS  PubMed  Google Scholar 

  • Fan HY, Sun QY (2004) Involvement of mitogen-activated protein kinase cascade during oocyte maturation and fertilization in mammals. Biol Reprod 70(3):535–547. doi:10.1095/biolreprod.103.022830

    Article  CAS  PubMed  Google Scholar 

  • Fang H, Wu Y, Guo J et al (2012) T-2 toxin induces apoptosis in differentiated murine embryonic stem cells through reactive oxygen species-mediated mitochondrial pathway. Apoptosis 17(8):895–907. doi:10.1007/s10495-012-0724-3

    Article  CAS  PubMed  Google Scholar 

  • Glavits R, Sandor GS, Vanyi A, Gajdacs G (1983) Reproductive disorders caused by trichothecene mycotoxins in a large-scale pig herd. Acta Vet Hung 31(4):173–180

    CAS  PubMed  Google Scholar 

  • Govin J, Dorsey J, Gaucher J, Rousseaux S, Khochbin S, Berger SL (2010) Systematic screen reveals new functional dynamics of histones H3 and H4 during gametogenesis. Genes Dev 24(16):1772–1786. doi:10.1101/gad.1954910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harvey AJ, Kind KL, Thompson JG (2002) REDOX regulation of early embryo development. Reproduction 123(4):479–486

    Article  CAS  PubMed  Google Scholar 

  • Hassold T, Hunt P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2(4):280–291. doi:10.1038/35066065

    Article  CAS  PubMed  Google Scholar 

  • Hirota T, Lipp JJ, Toh BH, Peters JM (2005) Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature 438(7071):1176–1180. doi:10.1038/nature04254

    Article  CAS  PubMed  Google Scholar 

  • Hou YJ, Xiong B, Zheng WJ et al (2014a) Oocyte quality in mice is affected by a mycotoxin-contaminated diet. Environ Mol Mutagen 55(4):354–362. doi:10.1002/em.21833

    Article  CAS  PubMed  Google Scholar 

  • Hou YJ, Zhu CC, Xu YX, Cui XS, Kim NH, Sun SC (2014b) Zearalenone exposure affects mouse oocyte meiotic maturation and granulosa cell proliferation. Environ Toxicol. doi:10.1002/tox.21995

    Google Scholar 

  • Huang P, Akagawa K, Yokoyama Y, Nohara K, Kano K, Morimoto K (2007) T-2 toxin initially activates caspase-2 and induces apoptosis in U937 cells. Toxicol Lett 170(1):1–10. doi:10.1016/j.toxlet.2006.05.017

    Article  CAS  PubMed  Google Scholar 

  • Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, Funabiki H (2010) Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science 330(6001):235–239. doi:10.1126/science.1189505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klotzel M, Gutsche B, Lauber U, Humpf HU (2005) Determination of 12 type A and B trichothecenes in cereals by liquid chromatography–electrospray ionization tandem mass spectrometry. J Agric Food Chem 53(23):8904–8910. doi:10.1021/jf051501c

    Article  PubMed  Google Scholar 

  • Lafarge-Frayssinet C, Chakor K, Lafont P, Frayssinet C (1990) Transplacental transfer of T2-toxin: pathological effect. J Environ Pathol Toxicol Oncol 10(1–2):64–68

    CAS  PubMed  Google Scholar 

  • Lautraite S, Parent-Massin D, Rio B, Hoellinger H (1995) Comparison of toxicity induced by T-2 toxin on human and rat granulo-monocytic progenitors with an in vitro model. Hum Exp Toxicol 14(8):672–678

    Article  CAS  PubMed  Google Scholar 

  • Lee SE, Hwang KC, Sun SC, Xu YN, Kim NH (2011) Modulation of autophagy influences development and apoptosis in mouse embryos developing in vitro. Mol Reprod Dev 78(7):498–509. doi:10.1002/mrd.21331

    Article  CAS  PubMed  Google Scholar 

  • Lees-Murdock DJ, Shovlin TC, Gardiner T, De Felici M, Walsh CP (2005) DNA methyltransferase expression in the mouse germ line during periods of de novo methylation. Dev Dyn 232(4):992–1002. doi:10.1002/dvdy.20288

    Article  CAS  PubMed  Google Scholar 

  • Li G, Shinozuka J, Uetsuka K, Nakayama H, Doi K (1997) T-2 toxin-induced apoptosis in intestinal crypt epithelial cells of mice. Exp Toxicol Pathol 49(6):447–450. doi:10.1016/S0940-2993(97)80132-7

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Trimarchi JR, Keefe DL (2000) Involvement of mitochondria in oxidative stress-induced cell death in mouse zygotes. Biol Reprod 62(6):1745–1753

    Article  CAS  PubMed  Google Scholar 

  • Malekinejad H, Schoevers EJ, Daemen IJ et al (2007) Exposure of oocytes to the Fusarium toxins zearalenone and deoxynivalenol causes aneuploidy and abnormal embryo development in pigs. Biol Reprod 77(5):840–847. doi:10.1095/biolreprod.107.062711

    Article  CAS  PubMed  Google Scholar 

  • Ohta M, Ishii K, Ueno Y (1977) Metabolism of trichothecene mycotoxins. I. Microsomal deacetylation of T-2 toxin in animal tissues. J Biochem 82(6):1591–1598

    CAS  PubMed  Google Scholar 

  • Parent-Massin D (2004) Haematotoxicity of trichothecenes. Toxicol Lett 153(1):75–81. doi:10.1016/j.toxlet.2004.04.024

    Article  CAS  PubMed  Google Scholar 

  • Schollenberger M, Muller HM, Rufle M, Suchy S, Plank S, Drochner W (2006) Natural occurrence of 16 fusarium toxins in grains and feedstuffs of plant origin from Germany. Mycopathologia 161(1):43–52. doi:10.1007/s11046-005-0199-7

    Article  PubMed  Google Scholar 

  • Schultz RM (2002) The molecular foundations of the maternal to zygotic transition in the preimplantation embryo. Hum Reprod Update 8(4):323–331

    Article  CAS  PubMed  Google Scholar 

  • Sehata S, Kiyosawa N, Atsumi F et al (2005) Microarray analysis of T-2 toxin-induced liver, placenta and fetal liver lesions in pregnant rats. Exp Toxicol Pathol 57(1):15–28. doi:10.1016/j.etp.2005.02.005

    Article  CAS  PubMed  Google Scholar 

  • Shinozuka J, Li G, Kiatipattanasakul W, Uetsuka K, Nakayama H, Doia K (1997) T-2 toxin-induced apoptosis in lymphoid organs of mice. Exp Toxicol Pathol 49(5):387–392. doi:10.1016/S0940-2993(97)80124-8

    Article  CAS  PubMed  Google Scholar 

  • Shinozuka J, Suzuki M, Noguchi N et al (1998) T-2 toxin-induced apoptosis in hematopoietic tissues of mice. Toxicol Pathol 26(5):674–681

    CAS  PubMed  Google Scholar 

  • Somoskoi B, Kovacs M, Cseh S (2014) Effects of T-2 mycotoxin on in vitro development and chromatin status of mouse embryos being in preimplantation stages. Toxicol Ind Health. doi:10.1177/0748233714555394

    PubMed  Google Scholar 

  • Song BS, Kim JS, Kim YH et al (2014) Induction of autophagy during in vitro maturation improves the nuclear and cytoplasmic maturation of porcine oocytes. Reprod Fertil Dev 26(7):974–981. doi:10.1071/RD13106

    Article  PubMed  Google Scholar 

  • Tamura H, Takasaki A, Miwa I et al (2008) Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res 44(3):280–287. doi:10.1111/j.1600-079X.2007.00524.x

    Article  CAS  PubMed  Google Scholar 

  • Tomizawa S, Nowacka-Woszuk J, Kelsey G (2012) DNA methylation establishment during oocyte growth: mechanisms and significance. Int J Dev Biol 56(10–12):867–875. doi:10.1387/ijdb.120152gk

    Article  CAS  PubMed  Google Scholar 

  • Van Blerkom J (2011) Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion 11(5):797–813. doi:10.1016/j.mito.2010.09.012

    Article  PubMed  Google Scholar 

  • Wang Y, Zheng W, Bian X et al (2014) Zearalenone induces apoptosis and cytoprotective autophagy in primary Leydig cells. Toxicol Lett 226(2):182–191. doi:10.1016/j.toxlet.2014.02.003

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Jing L, Yuan H, Peng SQ (2011) T-2 toxin induces apoptosis in ovarian granulosa cells of rats through reactive oxygen species-mediated mitochondrial pathway. Toxicol Lett 202(3):168–177. doi:10.1016/j.toxlet.2011.01.029

    Article  CAS  PubMed  Google Scholar 

  • Xu YN, Shen XH, Lee SE et al (2012) Autophagy influences maternal mRNA degradation and apoptosis in porcine parthenotes developing in vitro. J Reprod Dev 58(5):576–584

    Article  CAS  PubMed  Google Scholar 

  • Yagen B, Bialer M (1993) Metabolism and pharmacokinetics of T-2 toxin and related trichothecenes. Drug Metab Rev 25(3):281–323. doi:10.3109/03602539308993978

    Article  CAS  PubMed  Google Scholar 

  • Yuan G, Wang Y, Yuan X et al (2014) T-2 toxin induces developmental toxicity and apoptosis in zebrafish embryos. J Environ Sci (China) 26(4):917–925. doi:10.1016/S1001-0742(13)60510-0

    Article  CAS  Google Scholar 

  • Zhu CC, Hou YJ, Han J, Cui XS, Kim NH, Sun SC (2014a) Zearalenone exposure affects epigenetic modifications of mouse eggs. Mutagenesis 29(6):489–495. doi:10.1093/mutage/geu033

    Article  CAS  PubMed  Google Scholar 

  • Zhu CC, Hou YJ, Han J et al (2014b) Effect of mycotoxin-containing diets on epigenetic modifications of mouse oocytes by fluorescence microscopy analysis. Microsc Microanal 20(4):1158–1166. doi:10.1017/S1431927614000919

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Basic Research Program of China (2014CB138503) and the Natural Science Foundation of Jiangsu Province (BK20140030).

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  1. College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China

    Cheng-Cheng Zhu, Yue Zhang, Xing Duan, Jun Han & Shao-Chen Sun

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  1. Cheng-Cheng Zhu
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Zhu, CC., Zhang, Y., Duan, X. et al. Toxic effects of HT-2 toxin on mouse oocytes and its possible mechanisms. Arch Toxicol 90, 1495–1505 (2016). https://doi.org/10.1007/s00204-015-1560-3

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