Mycotoxin Research

, Volume 34, Issue 2, pp 99–106 | Cite as

Exposure of pregnant sows to deoxynivalenol during 35–70 days of gestation does not affect pathomorphological and immunohistochemical properties of fetal organs

  • Wolf Wippermann
  • Anne Heckmann
  • Kathrin Jäger
  • Sven Dänicke
  • Heinz-Adolf Schoon
Original Article
  • 63 Downloads

Abstract

In order to evaluate the influence of deoxynivalenol (DON) on histomorphological and immunohistochemical parameters in the development of porcine fetuses, five pregnant sows were fed a control diet (0.15 mg DON/kg diet) and seven sows a contaminated diet (4.42 mg DON/kg diet) between days 35 and 70 of gestation. On day 70, fetuses were delivered by caesarean section and sows and fetuses were euthanized. Tissue samples of three fetuses from each sow were collected, fixed in formalin, and processed routinely for light microscopy and immunohistochemistry. At necropsy, no macroscopic lesions were observed in any organ of the fetuses. Histomorphological, immunohistochemical, and morphometrical parameters of the immune system, liver, and intestinal tract were examined. The following antibodies were used in the liver, spleen, lymph nodes, thymus, gut, and bone marrow to compare control- and DON-treated animals: (I) CD3 and CD79a (T and B lymphocytes differentiation); (II) myeloid/histiocyte antigen 387 (MAC) (identification of macrophages); (III) Ki-67 Antigen (Ki-67) (proliferation marker); (IV) p-p-38 mitogen-activated protein kinases (p-p38 MAPK) as well as caspase-3 (cas3) and caspase-9 (cas9) (enzymes of apoptosis cascade); (V) tumor necrosis factor-alpha (TNFα) (immune-related protein). The results of the study show that exposure of pregnant sows with DON between gestation days 35 and 70 causes no pathomorphologically or immunohistochemically detectable alterations in all fetal organs examined.

Keywords

Deoxynivalenol Fusarium toxins Histology Immunohistochemistry Porcine Fetus 

Notes

Compliance with ethical standards

The present study was approved by the Committee for Animal Use and Care of the Ministerial Agricultural Department of Mecklenburg-Western Pomerania (local country of experiment stable; reference number: LVL M-V/310-4/7221.3-1.1-006/0), Germany, according to the German Law for Animal Protection (TierSchG).

Conflicts of interest

None. The authors have full control of all primary data and allow the journal to review the data if requested.

References

  1. Appelgren LE, Arora RG, Larsson P, (1982) Autoradiographic studies of [3H]zearalenone in mice. Toxicology 25 (2–3):243–253.  https://doi.org/10.1016/0300-483X(82)90033-6
  2. Arnold DL, McGuire PF, Nera EA, Karpinski KF, Bickis MG, Zawidzka ZZ, Vernie S, Vesonder RF (1986) The toxicity of orally administered deoxynivalenol (vomitoxin) in rats and mice. Food Chem Toxicol 24(9):935–941.  https://doi.org/10.1016/0278-6915(86)90321-2 CrossRefPubMedGoogle Scholar
  3. Awad WA, Bohm J, Razzazi-Fazeli E, Ghareeb K, Zentek J (2006a) Effect of addition of a probiotic microorganism to broiler diets contaminated with deoxynivalenol on performance and histological alterations of intestinal villi of broiler chickens. Poult Sci 85(6):974–979.  https://doi.org/10.1093/ps/85.6.974 CrossRefPubMedGoogle Scholar
  4. Awad WA, Böhm J, Razzazi-Fazeli E, Zentek J (2006b) Effects of feeding deoxynivalenol contaminated wheat on growth performance, organ weights and histological parameters of the intestine of broiler chickens. J Anim Physiol Anim Nutr (Berl) 90(1-2):32–37.  https://doi.org/10.1111/j.1439-0396.2005.00616.x CrossRefGoogle Scholar
  5. Böck P (1989) Farben der Schnitt. In: Böck P (ed) Romeis-Mikroskopische Technik, 17th edn. Verlag Urban und Schwarzenberg, Wien, pp 197–249Google Scholar
  6. Chianini F, Majó N, Segalés J, Domínguez J, Domingo M (2001) Immunohistological study of the immune system cells in paraffin-embedded tissues of conventional pigs. Vet Immunol Immunopathol 82(3-4):245–255.  https://doi.org/10.1016/S0165-2427(01)00364-6 CrossRefPubMedGoogle Scholar
  7. Chowdhury SR, Smith TK (2005) Effects of feeding grains naturally contaminated with Fusarium mycotoxins on hepatic fractional protein synthesis rates of laying hens and the efficacy of a polymeric glucomannan mycotoxin adsorbent. Poult Sci 84(11):1671–1674.  https://doi.org/10.1093/ps/84.11.1671 CrossRefPubMedGoogle Scholar
  8. Chung YJ, Zhou HR, Pestka JJ (2003) Transcriptional and posttranscriptional roles for p38 mitogen-activated protein kinase in upregulation of TNF-alpha expression by deoxynivalenol (vomitoxin). Toxicol Appl Pharmacol 193(2):188–201.  https://doi.org/10.1016/S0041-008X(03)00299-0 CrossRefPubMedGoogle Scholar
  9. Cundliffe E, Davies JE (1977) Inhibition of initiation, elongation, and termination of eukaryotic protein-synthesis by trichothecene fungal toxins. Antimicrob Agents Chemother 11(3):491–499.  https://doi.org/10.1128/AAC.11.3.491 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dänicke S, Brüssow KP, Goyarts T, Valenta H, Ueberschär KH, Tiemann U (2007) On the transfer of the fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) from the sow to the full-term piglet during the last third of gestation. Food Chem Toxicol 45(9):1565–1574.  https://doi.org/10.1016/j.fct.2007.02.016 CrossRefPubMedGoogle Scholar
  11. De Botton S, Sabri S, Daugas E, Zermati Y, Guidotti JE, Hermine O, Kroemer G, Vaincheker W, Debili N (2001) Platelet formation is the consequence of caspase activation within megakaryocytes. Blood 100(4):1310–1317.  https://doi.org/10.1182/blood-2002-03-0686 CrossRefGoogle Scholar
  12. Ehrlich KC, Daigle KW (1987) Protein synthesis inhibition by 8-oxo-12,13-epoxytrichothecenes. Biochim Biophys Acta 923(2):206–213.  https://doi.org/10.1016/0304-4165(87)90005-5 CrossRefPubMedGoogle Scholar
  13. Ellenberger C, Wilsher S, Allen WR, Hoffmann C, Kolling M, Bazer FW, Klug J, Schoon D, Schoon HA (2008) Immunolocalisation of the uterine secretory proteins uterocalin, uteroferrin and uteroglobin in the mare’s uterus and placenta throughout pregnancy. Theriogenology 70(5):746–757.  https://doi.org/10.1016/.jtheriogenology.2008.04.050 CrossRefPubMedGoogle Scholar
  14. Fichelson S, Freyssinier JM, Picard F, Fontenay-Roupie M, Guesnu M, Cherai M, Gisselbrecht S, Porteu F (1999) Megakaryocyte growth and development factor-induced proliferation and differentiation are regulated by the mitogen-activated protein kinase pathway in primitive cord blood hematopoietic progenitors. Blood 94(5):1601–1613PubMedGoogle Scholar
  15. Gerez JR, Pinton P, Callu P, Grosjean F, Oswald IP, Bracarense AP (2015) Deoxynivalenol alone or in combination with nivalenol and zearalenone induce systemic histological changes in pigs. Exp Toxicol Pathol 67(2):89–98.  https://doi.org/10.1016/j.etp.2014.10.001 CrossRefPubMedGoogle Scholar
  16. Goyarts T, Dänicke S, Brüssow KP, Valenta H, Ueberschär KH, Tiemann U (2007) On the transfer of the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) from sows to their fetuses during days 35-70 of gestation. Toxicol Lett 171(1–2):38–49.  https://doi.org/10.1016/j.toxlet.2007.04.003 CrossRefPubMedGoogle Scholar
  17. Goyarts T, Brüssow KP, Valenta H, Tiemann U, Jäger K, Dänicke S (2010) On the effects of the Fusarium toxin deoxynivalenol (DON) administered per os or intraperitoneal infusion to sows during days 63 to 70 of gestation. Mycotoxin Res 26(2):119–131.  https://doi.org/10.1007/s12550-010-0047-6 CrossRefPubMedGoogle Scholar
  18. Knight JW, Bazer FW, Thatcher WW, Franke DE, Wallace HD (1977) Conceptus development in intact and unilaterally hysterectomized-ovariectomized gilts: interrelations among hormonal status, placental development, fetal fluids and fetal growth. J Anim Sci 44(4):620–637.  https://doi.org/10.2527/jas1977.444620x CrossRefPubMedGoogle Scholar
  19. Lim SK, Jeong YW, Kim DI, Park MJ, Choi JH, Kim SU, Kang SS, Han HJ, Park SH (2013) Activation of PRMT1 and PRMT5 mediates hypoxia- and ischemia-induced apoptosis in human lung epithelial cells and the lung of miniature pigs: the role of p38 and JNK mitogen-activated protein kinases. Biochem Biophys Res Commun 440(4):707–713.  https://doi.org/10.1016/j.bbrc.2013.09.136 CrossRefPubMedGoogle Scholar
  20. Özgen S, Rasch K, Kropp G, Schoon HA, Aupperle H, Sieme H, Klug E (1997) Aetiopathogenesis and therapy of equine hydromucometra: preliminary data. Pferdeheilkunde 13:533–534Google Scholar
  21. Perez J, García PM, Bautista MJ, Millán Y, Ordás J, Martín de las Mulas J (2002) Immunohistochemical characterization of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic tumors of Duroc and Iberian swine. Vet Pathol 39(4):445–451.  https://doi.org/10.1354/vp.39-4-445 CrossRefPubMedGoogle Scholar
  22. Pestka JJ (2008) Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Addit Contam 24(9):1–13.  https://doi.org/10.1080/02652030802056626 Google Scholar
  23. Pestka JJ, Zhou HR, Moon Y, Chung YJ (2004) Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicol Lett 153(1):61–73.  https://doi.org/10.1016/j.toxlet.2004.04.023 CrossRefPubMedGoogle Scholar
  24. Redondo E, Masot AJ, Fernández A, Gázquez A (2009) Histopathological and immunohistochemical findings in the lungs of pigs infected experimentally with Mycoplasma hyopneumoniae. Comp Pathol 140(4):260–270.  https://doi.org/10.1016/j.jcpa.2008.12.008 CrossRefGoogle Scholar
  25. Richter J (1902) Vergleichende Untersuchungen über den mikroskopischen Bau der Lymphdrüsen von Pferd, Rind, Schwein und Hund. Arch f mikr Anat 60(1):469–514.  https://doi.org/10.1007/BF02978396 CrossRefGoogle Scholar
  26. Sinkora M, Butler JE (2009) The ontogeny of the porcine immune system. Dev Comp Immunol 33(3):273–283.  https://doi.org/10.1016/j.dci.2008.07.011 CrossRefPubMedGoogle Scholar
  27. Tang S, Dong X, Zhang W (2014) Obestatin changes proliferation, differentiation and apoptosis of porcine preadipocytes. Ann Endocrinol (Paris) 75(1):1–9.  https://doi.org/10.1016/j.ando.2013.10.003 CrossRefGoogle Scholar
  28. The Commission of the European Communities (2006) Commission recommendation of 17 August 2006: on the presence of deoxynivalenol, zearalenone, ochratoxin A, T-2 and HT-2 and fumonisin in products intended for animal feeding. Off J European Union L229:7–9Google Scholar
  29. Tiemann U, Brüssow KP, Dannenberger D, Jonas L, Pöhland R, Jager K, Daenicke S, Hagemann E (2008) The effect of feeding a diet naturally contaminated with deoxynivalenol (DON) and zearalenone (ZON) on the spleen and liver of sow and fetus from day 35 to 70 of gestation. Toxicol Lett 179(3):113–117.  https://doi.org/10.1016/j.toxlet.2008.04.016 CrossRefPubMedGoogle Scholar
  30. Tuleta I, Bauriedel G, Steinmetz M, Pabst S, Peuster M, Welsch U, Nickenig G, Skowasch D (2010) Apoptosis-regulated survival of primarily extravascular cells in proliferative active poststent neointima. Cardiovasc Pathol 19(6):353–360.  https://doi.org/10.1016/j.carpath.2009.07.006 CrossRefPubMedGoogle Scholar
  31. Zhou HR, Yan D, Pestka JJ (1997) Differential cytokine mRNA expression in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): dose response and time course. Toxicol Appl Pharmacol 144(2):294–305.  https://doi.org/10.1006/taap.1997.8132 CrossRefPubMedGoogle Scholar
  32. Zhou HR, Harkema JR, Hotchkiss JA, Yan D, Roth RA, Pestka JJ (2000) Lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) synergistically induce apoptosis in murine lymphoid organs. Toxicol Sci 53(2):253–263.  https://doi.org/10.1093/toxsci/53.2.253 CrossRefPubMedGoogle Scholar
  33. Zhou HR, Islam Z, Pestka JJ (2003) Rapid, sequential activation of mitogen-activated protein kinases and transcription factors precedes proinflammatory cytokine mRNA expression in spleens of mice exposed to the trichothecene vomitoxin. Toxicol Sci 72(1):130–142.  https://doi.org/10.1093/toxsci/kfg006 CrossRefPubMedGoogle Scholar
  34. Zhou HR, Islam Z, Pestka JJ (2005) Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol. Toxicol Sci 87(1):113–122.  https://doi.org/10.1039/toxsci/kfi234. CrossRefPubMedGoogle Scholar

Copyright information

© Society for Mycotoxin Research and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Wolf Wippermann
    • 1
    • 2
  • Anne Heckmann
    • 1
  • Kathrin Jäger
    • 1
  • Sven Dänicke
    • 3
  • Heinz-Adolf Schoon
    • 1
  1. 1.Institute of Pathology of the Faculty of Veterinary MedicineUniversity of LeipzigLeipzigGermany
  2. 2.Clinic for Ruminants and Swine of the Faculty of Veterinary MedicineUniversity of LeipzigLeipzigGermany
  3. 3.Institute of Animal NutritionFederal Research Centre for Animal Health (FLI)BraunschweigGermany

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