Desoxinivalenol durante período pré-puberal induz apoptose em ovários de ratas imaturas

Autores

DOI:

https://doi.org/10.5433/1679-0359.2023v44n5p1621

Palavras-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.

Métricas

Carregando Métricas ...

Biografia do Autor

Juliana Rubira Gerez, Universidade Estadual de Londrina

Profa. Dra., Laboratório de Patologia Animal, Departamento de Medicina Veterinária Preventiva, Universidade Estadual de Londrina, UEL, Londrina, PR, Brasil.

Gisele Augusta Amorim de Lemos, Universidade Estadual de Londrina

Pós-graduanda, Programa de Saúde Animal, UEL, Londrina, PR, Brasil.

Thaynara Camacho, Universidade Estadual de Londrina

Pós-graduanda em Medicina Veterinária, UEL, Londrina, PR, Brasil.

Victor Hugo Brunaldi Marutani, Universidade Estadual de Londrina

Pós-graduanda, Programa de Saúde Animal, UEL, Londrina, PR, Brasil.

Luiz Gustavo Chuffa, Universidade Estadual Paulista

Prof. Dr., Departamento de Biologia Estrutural e Funcional, Universidade Estadual Paulista, UNESP, Botucatu, SP, Brasil.

Henrique Spaulonci Silveira, Universidade Estadual Paulista

Pesquisador, Departamento de Biologia Estrutural e Funcional, UNESP, Botucatu, SP, Brasil.

Waldiceu Aparecido Verri , Universidade Estadual de Londrina

Prof. Dr., Laboratório de Dor, Inflamação, Neuropatia e Câncer, Departamento de Ciências Patológicas, UEL, Londrina, PR, Brasil.

Eduardo Micotti da Gloria, Universidade de São Paulo

Pesquisador, Laboratório de Micologia, Universidade de São Paulo, USP, Pirassununga, SP, Brasil.

Ana Paula Frederico Rodrigues Loureiro Bracarence, Universidade Estadual de Londrina

Profa. Dra., Laboratório de Patologia Animal, Departamento de Medicina Veterinária Preventiva, Universidade Estadual de Londrina, UEL, Londrina, PR, Brasil.

Referências

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

Downloads

Publicado

2023-11-06

Como Citar

Gerez, J. R., Lemos, G. A. A. de, Camacho, T., Marutani, V. H. B., Chuffa, L. G., Silveira, H. S., Verri , W. A., Gloria, E. M. da, & Bracarence, A. P. F. R. L. (2023). Desoxinivalenol durante período pré-puberal induz apoptose em ovários de ratas imaturas. Semina: Ciências Agrárias, 44(5), 1621–1636. https://doi.org/10.5433/1679-0359.2023v44n5p1621

Edição

Seção

Artigos

Artigos mais lidos pelo mesmo(s) autor(es)