Desoxinivalenol durante período pré-puberal induz apoptose em ovários de ratas imaturas
DOI:
https://doi.org/10.5433/1679-0359.2023v44n5p1621Palavras-chave:
Apoptose, Desoxinivalenol, Integridade folicular, Ovário, Ratos.Resumo
A puberdade é um processo regulado pelo sistema endócrino em que as diversas alterações fisiológicas e biológicas são responsáveis pelo início das funções reprodutivas em animais e humanos. DON pode interferir no sistema hormonal induzindo desordens endócrinas e danos reprodutivos. Entretanto, o potencial de DON em causar danos reprodutivos no período da puberdade tem sido negligenciado. Considerando que crianças e adolescentes têm um alto risco de exposição à DON, este estudo teve como objetivo avaliar o efeito desta micotoxina durante a puberdade sobre a integridade folicular e a expressão de proteínas pró-apoptóticas (BAX e Caspase-3) e anti-apoptóticas (BCL-2) em ovários de ratos jovens. Dez ratos Wistar pré-púberes (28 dias de idade) foram utilizados. Os animais foram expostos por 28 dias às seguintes dietas: 1) controle: dieta livre de micotoxinas e 2) DON: dieta contendo 10 mg DON/Kg de alimento. Ao final, os ovários e úteros foram pesados e os ovários submetidos à análise morfométrica e imuno-histoquímica. A ingestão da dieta contaminada induziu a uma redução significativa no peso dos ovários e úteros, no entanto não houve diferença no número de folículos ovarianos em todos os estágios de desenvolvimento folicular. Um aumento significativo da expressão de BAX e Caspase-3 e uma diminuição da expressão de BCL-2 foram observados na maioria dos estágios foliculares e do corpo lúteo nos animais alimentados com DON. Em conclusão, a exposição ao DON durante o período pré-púbere induz apoptose em diferentes populações de células ovarianas e pode interferir no desenvolvimento reprodutivo de animais adultos.
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Alm, H., Greising, T., Brüssow, K. P., 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. Toxicology In Vitro, 16(6), 643-648. doi: 10.1016/s0887-2333(02)00059-0 DOI: https://doi.org/10.1016/S0887-2333(02)00059-0
Andretta, I., Kipper, M., Lehnen, C. R., Hauschild, L., Vale, M. M., & Lovatto, P. A. (2012). Meta-analytical study of productive and nutritional interactions of mycotoxins in growing pigs. Animal, 6(9), 1476-1482. doi: 10.1017/s1751731111002278 DOI: https://doi.org/10.1017/S1751731111002278
Bracarense, A. P. F., Basso, K. M., Silva, E. O. da, Payros, D., & Oswald, I. P. (2017). Deoxynivalenol in the liver and lymphoid organs of rats: effects of dose and duration on immunohistological changes. World Mycotoxin Journal, 10(1), 89-96. doi: 10.3920/WMJ2016.2094 DOI: https://doi.org/10.3920/WMJ2016.2094
Chuffa, L. G., Alves, M. S., Martinez, M., Camargo, I. C., Pinheiro, P. F., Domeniconi, R. F., Júnior, L. A. L., & Martinez, F. E. (2016). Apoptosis is triggered by melatonin in an in vivo model of ovarian carcinoma. Endocrine-Related Cancer, 23(2), 65-76. doi: 10.1530/erc-15-0463 DOI: https://doi.org/10.1530/ERC-15-0463
Clark, E. S., Flannery, B. M., & Pestka, J. J. (2015). Murine anorectic response to deoxynivalenol (vomitoxin) is sex-dependent. Toxins, 7(8), 2845-2859. doi: 10.3390/toxins7082845 DOI: https://doi.org/10.3390/toxins7082845
Da Broi, M. G., Giorgi, V. S. I., Wang, F., Keefe, D. L., Albertini, D., Navarro, P. A. (2018). Influence of follicular fluid and cumulus cells on oocyte quality: clinical implications. Journal of Assisted Reproduction and Genetics, 35(5), 735-751. doi: 10.1007/s10815-018-1143-3 DOI: https://doi.org/10.1007/s10815-018-1143-3
Dai, Y., Xie, H., & Xu, Y. (2017). Evaluation of deoxynivalenol-induced toxic effects on mouse endometrial stromal cells: cell apoptosis and cell cycle. Biochemical and Biophysical Research Communications, 483(1), 572-577. doi: 10.1016/j.bbrc.2016.12.103 DOI: https://doi.org/10.1016/j.bbrc.2016.12.103
De Santis, B., Debegnach, F., Miano, B., Moretti, G., Sonego, E., Chiaretti, A., Buonsenso, D., & Brera, C. (2019). Determination of deoxynivalenol biomarkers in Italian urine samples. Toxins, 11(8), 441-456. doi: 10.3390/toxins11080441 DOI: https://doi.org/10.3390/toxins11080441
Deng, C., Li, C., Zhou, S., Wang, X., Xu, H., Wang, D., Gong, Y. Y., Routledge, M. N., Zhao, Y., & Wu, Y. (2018). Risk assessment of deoxynivalenol in high-risk area of China by human biomonitoring using an improved high throughput UPLC-MS/MS method. Scientific Reports, 8(1), 3901. doi: 10.1038/s41598-018-22206-y DOI: https://doi.org/10.1038/s41598-018-22206-y
Eze, U., Routledge, M., Okonofua, F., Huntriss, J., & Gong, Y. (2018). Mycotoxin exposure and adverse reproductive health outcomes in Africa: a review. World Mycotoxin Journal, 11(3), 321-339. doi: 10.3920/WMJ2017.2261 DOI: https://doi.org/10.3920/WMJ2017.2261
Friend, D. W., Trenholm, H. L., Fiser, P. S., Hartin, K. E., & Thompson, B. K. (1986). Effect of feeding diets containing deoxynivalenol (vomitoxin)-contaminated wheat or corn on the feed consumption, weight gain, organ weight and sexual development of male and female pigs. Canadian Journal of Animal Science, 66(3), 765-775. doi: 10.4141/cjas86-083 DOI: https://doi.org/10.4141/cjas86-083
Gerez, J. R., Camacho, T., Marutani, V. H. B., Nascimento de Matos, R. L., Hohmann, M. S., Verri, W. A., Jr., & Bracarense, A. (2021). Ovarian toxicity by fusariotoxins in pigs: Does it imply in oxidative stress? Theriogenology, 165, 84-91. doi: 10.1016/j.theriogenology.2021.02.003 DOI: https://doi.org/10.1016/j.theriogenology.2021.02.003
Gerez, J. R., Desto, S. S., & Bracarense, A. P. F. R. L. (2017). Deoxynivalenol induces toxic effects in the ovaries of pigs: An ex vivo approach. Theriogenology, 90, 94-100. doi: 10.1016/j.theriogenology.2016.10.023 DOI: https://doi.org/10.1016/j.theriogenology.2016.10.023
Grenier, B., & Applegate, T. J. (2013). Modulation of intestinal functions following mycotoxin ingestion: meta-analysis of published experiments in animals. Toxins, 5(2), 396-430. doi: 10.3390/toxins5020396 DOI: https://doi.org/10.3390/toxins5020396
Guerrero-Netro, H. M., Chorfi, Y., & Price, C. A. (2015). Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells. Reproduction, 149(6), 555-561. doi: 10.1530/rep-15-0018 DOI: https://doi.org/10.1530/REP-15-0018
Han, J., Wang, Q. C., Zhu, C. C., Liu, J., Zhang, Y., Cui, X. S., Kim, N. H., & Sun, S. C. (2016). Deoxynivalenol exposure induces autophagy/apoptosis and epigenetic modification changes during porcine oocyte maturation. Toxicology and Applied Pharmacology, 300, 70-76. doi: 10.1016/j.taap.2016.03.006 DOI: https://doi.org/10.1016/j.taap.2016.03.006
Iverson, F., Armstrong, C., Nera, E., Truelove, J., Fernie, S., Scott, P., Stapley, R., Hayward, S., & Gunner, S. (1995). Chronic feeding study of deoxynivalenol in B6C3F1 male and female mice. Teratogenesis, Carcinogenesis, and Mutagenesis, 15(6), 283-306. doi: 10.1002/(sici)1520-6866(1996)15:6<283::aid-tcm5>3.0.co;2-e DOI: https://doi.org/10.1002/tcm.1770150606
Knutsen, H. K., Alexander, J., Barregård, L., Bignami, M., Brüschweiler, B., Ceccatelli, S., Cottrill, B., Dinovi, D., Grasl-Kraupp, B., Hogstrand, C., Hoogenboom, L., Nebbia, C. S., Oswald, I. P., Petersen, A., Rose, M., Roudot, A. C., Schwerdtle, T., Vleminckz, C., Vollmer, G.,... & Grasl‐Kraupp, B. (2018). Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified formsin food and feed. EFSA Journal, 15(9), e04718. doi: 10.2903/j.efsa.2017 DOI: https://doi.org/10.2903/j.efsa.2017.4851
Kolesárová, A., Capcarová, M., Maruniaková, N., Baková, Z., Toman, R., Nath, S., & Sirotkin, A. V. (2012). Deoxynivalenol-induced animal ovarian signaling: proliferation and apoptosis. Journal of Microbiology, Biotechnology and Food Sciences, 9(4), 323-332.
Laffan, S. B., Posobiec, L. M., Uhl, J. E., & Vidal, J. D. (2018). species comparison of postnatal development of the female reproductive system. Birth Defects Research, 110(3), 163-189. doi: 10.1002/bdr2.1132 DOI: https://doi.org/10.1002/bdr2.1132
Lan, M., Han, J., Pan, M. H., Wan, X., Pan, Z. N., & Sun, S. C. (2018). Melatonin protects against defects induced by deoxynivalenol during mouse oocyte maturation. Journal of Pineal Research, 65(1), e12477.doi: 10.1111/jpi.12477 DOI: https://doi.org/10.1111/jpi.12477
Lattanzio, V. M. T., Solfrizzo, M., De Girolamo, A., Chulze, S. N., Torres, A. M., & Visconti, A. (2011). LC–MS/MS characterization of the urinary excretion profile of the mycotoxin deoxynivalenol in human and rat. Journal of Chromatography B, 879(11), 707-715. doi: 10.1016/j.jchromb.2011.01.029 DOI: https://doi.org/10.1016/j.jchromb.2011.01.029
Liew, S. H., Nguyen, Q.-N., Strasser, A., Findlay, J. K., & Hutt, K. J. (2017). The ovarian reserve is depleted during puberty in a hormonally driven process dependent on the pro-apoptotic protein BMF. Cell Death & Disease, 8(8), e2971-e2971. doi: 10.1038/cddis.2017.361 DOI: https://doi.org/10.1038/cddis.2017.361
Lucioli, J., Pinton, P., Callu, P., Laffitte, J., Grosjean, F., Kolf-Clauw, M., Oswald, I. P., & Bracarense, A. P. (2013). The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: interest of ex vivo models as an alternative to in vivo experiments. Toxicon, 66, 31-36. doi: 10.1016/j.toxicon.2013.01.024 DOI: https://doi.org/10.1016/j.toxicon.2013.01.024
Malekinejad, H., Schoevers, E. J., Daemen, I. J., Zijlstra, C., Colenbrander, B., Fink-Gremmels, J., & Roelen, B. A. (2007). Exposure of oocytes to the Fusarium toxins zearalenone and deoxynivalenol causes aneuploidy and abnormal embryo development in pigs. Biology of Reproduction, 77(5), 840-847. doi: 10.1095/biolreprod.107.062711 DOI: https://doi.org/10.1095/biolreprod.107.062711
Maranghi, F., & Mantovani, A. (2012). Targeted toxicological testing to investigate the role of endocrine disrupters in puberty disorders. Reproductive Toxicology, 33(3), 290-296. doi: 10.1016/j.reprotox.2012.01.009 DOI: https://doi.org/10.1016/j.reprotox.2012.01.009
Massart, F., & Saggese, G. (2010). Oestrogenic mycotoxin exposures and precocious pubertal development. International Journal of Andrology, 33(2), 369-376. doi: 10.1111/j.1365-2605.2009.01009.x DOI: https://doi.org/10.1111/j.1365-2605.2009.01009.x
Massart, F., Meucci, V., Saggese, G., & Soldani, G. (2008). High growth rate of girls with precocious puberty exposed to estrogenic mycotoxins. The Journal of Pediatrics, 152(5), 690-695. doi: 10.1016/j.jpeds.2007.10.020 DOI: https://doi.org/10.1016/j.jpeds.2007.10.020
Medvedova, M., Kolesarova, A., Capcarova, M., Labuda, R., Sirotkin, A. V., Kovacik, J., & Bulla, J. (2011). The effect of deoxynivalenol on the secretion activity, proliferation and apoptosis of porcine ovarian granulosa cells in vitro. Journal of Environmental Science and Health, 46(3), 213-219. doi: 10.1080/03601234.2011.540205 DOI: https://doi.org/10.1080/03601234.2011.540205
Mishra, S., Srivastava, S., Dewangan, J., Divakar, A., & Kumar Rath, S. (2020). Global occurrence of deoxynivalenol in food commodities and exposure risk assessment in humans in the last decade: a survey. Critical Reviews in Food Science and Nutrition, 60(8), 1346-1374. doi: 10.1080/10408398.2019.1571479 DOI: https://doi.org/10.1080/10408398.2019.1571479
Morrissey, R. E. (1984). Teratological study of Fischer rats fed diet containing added vomitoxin. Food and Chemical Toxicology, 22(6), 453-457. doi: 10.1016/0278-6915(84)90328-4 DOI: https://doi.org/10.1016/0278-6915(84)90328-4
Morrissey, R. E., & Vesonder, R. F. (1985). Effect of deoxynivalenol (vomitoxin) on fertility, pregnancy, and postnatal development of Sprague-Dawley rats. Applied and Environmental Microbiology, 49(5), 1062-1066. doi: 10.1128/aem.49.5.1062-1066.1985 DOI: https://doi.org/10.1128/aem.49.5.1062-1066.1985
Ojeda, S. R., Andrews, W. W., Advis, J. P., & White, S. S. (1980). Recent advances in the endocrinology of puberty. Endocrine Reviews, 1(3), 228-257. doi: 10.1210/edrv-1-3-228 DOI: https://doi.org/10.1210/edrv-1-3-228
Papageorgiou, M., Wells, L., Williams, C., White, K., De Santis, B., Liu, Y., Debegnach, F., Miano, B., Moretti, G., Greetham, S., Brera, C., Atkin, S. L., Hardie, L. J., & Sathyapalan, T. (2018). Assessment of urinary deoxynivalenol biomarkers in UK children and adolescents. Toxins, 10(2), 50-62. doi: 10.3390/toxins10020050 DOI: https://doi.org/10.3390/toxins10020050
Pedersen, T., & Peters, H. (1968). Proposal for a classification of oocytes and follicles in the mouse ovary. Reproduction, 17(3), 555-557. doi: 10.1530/jrf.0.0170555 DOI: https://doi.org/10.1530/jrf.0.0170555
Pestka, J. J., & Smolinski, A. T. (2005). Deoxynivalenol: toxicology and potential effects on humans. Journal of Toxicology and Environmental Health, 8(1), 39-69. doi: 10.1080/10937400590889458 DOI: https://doi.org/10.1080/10937400590889458
Ranzenigo, G., Caloni, F., Cremonesi, F., Aad, P. Y., & Spicer, L. J. (2008). Effects of fusarium mycotoxins on steroid production by porcine granulosa cells. Animal Reproduction Science, 107(1-2), 115-130. doi: 10.1016/j.anireprosci.2007.06.023 DOI: https://doi.org/10.1016/j.anireprosci.2007.06.023
Rotter, B. A., Thompson, B. K., & Rotter, R. G. (1994). Optimization of the mouse bioassay for deoxynivalenol as an alternative to large animal studies. Bulletin of Environmental Contamination and Toxicology, 53(5), 642-647. doi: 10.1007/bf00196934 DOI: https://doi.org/10.1007/BF00196934
Schoevers, E. J., Fink-Gremmels, J., Colenbrander, B., & Roelen, B. A. J. (2010). Porcine oocytes are most vulnerable to the mycotoxin deoxynivalenol during formation of the meiotic spindle. Theriogenology, 74(6), 968-978. doi: 10.1016/j.theriogenology.2010.04.026 DOI: https://doi.org/10.1016/j.theriogenology.2010.04.026
Shi, D., Zhou, J., Zhao, L., Rong, X., Fan, Y., Hamid, H., Li, W., Ji, C., & Ma, Q. (2018). Alleviation of mycotoxin biodegradation agent on zearalenone and deoxynivalenol toxicosis in immature gilts. Journal of Animal Science and Biotechnology, 9(1), 42-52. doi: 10.1186/s40104-018-0255-z DOI: https://doi.org/10.1186/s40104-018-0255-z
Silva, M. V., Pante, G. C., Romoli, J. C. Z., Souza, A. P. M. de, Rocha, G., Ferreira, F. D., Feijó, A. L. R., Moscardi, S. M. P., Paula, K. R. de, Bando, R. Nerilo, S. B., & Machinski, M. Jr.(2018). Occurrence and risk assessment of population exposed to deoxynivalenol in foods derived from wheat flour in Brazil. Food Additives & Contaminants, 35(3), 546-554. doi: 10.1080/19440049.2017.1411613 DOI: https://doi.org/10.1080/19440049.2017.1411613
Sundheim, L., Lillegaard, I. T., Fæste, C. K., Brantsæter, A.-L., Brodal, G., & Eriksen, G. S. (2017). Deoxynivalenol exposure in Norway, risk assessments for different human age groups. Toxins, 9(2), 46-53. doi: 10.3390/toxins9020046 DOI: https://doi.org/10.3390/toxins9020046
Trenholm, H. L., Thompson, B. K., Foster, B. C., Charmley, L. L., Hartin, K. E., Coppock, R. W., & Albassam, M. A. (1994). Effects of feeding diets containing Fusarium (naturally) contaminated wheat or pure deoxynivalenol (DON) in growing pigs. Canadian Journal of Animal Science, 74(2), 361-369. doi: 10.4141/cjas94-049 DOI: https://doi.org/10.4141/cjas94-049
Yang, M., Wu, X., Zhang, W., Ye, P., Wang, Y., Zhu, W., Tao, Q., Xu, Y., Shang, J., Zhao, D., Ding, Y., Yin, Z., & Zhang, X. (2020). Transcriptional analysis of deoxynivalenol‐induced apoptosis of sow ovarian granulosa cell. Reproduction in Domestic Animals, 55(2), 217-228. doi: 10.1111/rda.13610 DOI: https://doi.org/10.1111/rda.13610
Yang, R., Wang, Y.-M., Zhang, L.-S., Zhang, L., Zhao, Z.-M., Zhao, J., & Peng, S.-Q. (2015). Delay of the onset of puberty in female rats by prepubertal exposure to T-2 toxin. Toxins, 7(11), 4668-4683. doi: 10.3390/toxins7114668 DOI: https://doi.org/10.3390/toxins7114668
Yu, M., Chen, L., Peng, Z., Nüssler, A. K., Wu, Q., Liu, L., & Yang, W. (2017). Mechanism of deoxynivalenol effects on the reproductive system and fetus malformation: current status and future challenges.Toxicology in Vitro, 41, 150-158. doi: 10.1016/j.tiv.2017.02.011 DOI: https://doi.org/10.1016/j.tiv.2017.02.011
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