Advertisement

Alternariol disturbs oocyte maturation and preimplantation development

  • Eric J. Schoevers
  • Regiane R. SantosEmail author
  • Bernard A. J. Roelen
Original Article

Abstract

Alternariol (AOH) is produced by fungi of the genus Alternaria and can be found in fruits, vegetables, and grains. Besides the oestrogenic activity demonstrated in vitro, this mycotoxin causes DNA damage and cell cycle arrest. Based on this, the effect of AOH was investigated on porcine female gametes during in vitro maturation and subsequent initial embryo development. A first experiment assessed a dose-response effect of AOH (5, 10, or 20 μmol/l) on cumulus expansion and in vitro oocyte nuclear maturation, in the presence or absence of follicular fluid (FF). A second experiment evaluated the effect of AOH (5, 10, or 20 μmol/l) exposure during porcine oocyte maturation, initial embryo development, or both periods, on preimplantation embryo development. Although FF protected oocytes from the deleterious effect of AOH, it did not avoid a decrease in cumulus cells expansion (5 μmol/l AOH regardless of the presence of FF). Moreover, exposure to AOH resulted in the degeneration of oocytes (10 μmol/l AOH in the absence of FF) and the occurrence of nuclear aberrations in mature oocytes (10 μmol/l AOH in the absence of FF and 20 μmol/l AOH in the presence of FF). Exposure to 5 μmol/l AOH during oocyte in vitro maturation was sufficient to impair initial embryo development.

Keywords

Porcine Female gametes Follicular fluid Cumulus expansion Embryos 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Abeydeera L, Day B (1997) In vitro penetration of pig oocytes in a modified Tris-buffered medium: effect of BSA, caffeine and calcium. Theriogenology 48:537–544CrossRefPubMedGoogle Scholar
  2. Aichinger G, Beisl J, Marko D (2017) Genistein and delphinidin antagonize the genotoxic effects of the mycotoxin alternariol in human colon carcinoma cells. Mol Nutr Food Res 61:2CrossRefGoogle Scholar
  3. Algriany O, Bevers M, Schoevers E, Colenbrander B, Dieleman S (2004) Follicle size-dependent effects of sow follicular fluid on in vitro cumulus expansion, nuclear maturation and blastocyst formation of sow cumulus oocytes complexes. Theriogenology 62:1483–1497CrossRefPubMedGoogle Scholar
  4. Bagg MA, Nottle MB, Armstrong DT, Grupen CG (2007) Relationship between follicle size and oocyte developmental competence in prepubertal and adult pigs. Reprod Fertil Dev 19:797–803CrossRefPubMedGoogle Scholar
  5. Bansal M, Singh N, Alam S, Pal S, Satyanarayana GNV, Singh D, Ansari KM (2019) Alternariol induced proliferation in primary mouse keratinocytes and inflammation in mouse skin is regulated via PGE2/EP2/cAMP/p-CREB signalling pathway. Toxicology 412:79–88CrossRefPubMedGoogle Scholar
  6. Burkhardt B, Pfeiffer E, Metzler M (2009) Absorption and metabolism of the mycotoxins alternariol and alternariol-9-methyl ether in Caco-2cells in vitro. Mycotoxin Res 25:149–157Google Scholar
  7. Bijttebier J, Tilleman K, Dhaenens M, Deforce D, Van Soom A, Maes D (2009) Comparative proteome analysis of porcine follicular fluid and serum reveals that excessive alpha(2)-macroglobulin in serum hampers successful expansion of cumulus-oocyte complexes. Proteomics 9:4554–4565CrossRefPubMedGoogle Scholar
  8. Carbone MC, Tatone C, Delle Monache S, Marci R, Caserta D, Colonna R, Amicarelli F (2003) Antioxidant enzymatic defences in human follicular fluid: characterization and age-dependent changes. Mol Hum Reprod 9:639–643CrossRefPubMedGoogle Scholar
  9. Daen FP, Sato E, Naito K, Toyoda Y (1994) The effect of pig follicular fluid fractions on cumulus expansion and male pronucleus formation in porcine oocytes matured and fertilized in vitro. J Reprod Fertil 101:667–673CrossRefPubMedGoogle Scholar
  10. Dellafiora L, Galaverna G, Cruciani G, Dall’Asta C (2019) A computational study toward the “personalized” activity of alternariol—does it matter for safe food at individual level? Food Chem Toxicol 130:199–206CrossRefPubMedGoogle Scholar
  11. EFSA (European Food Safety Authority), Arcella D, Eskola M, Gomez Ruiz JA (2016) Scientific report on the dietary exposure assessment to Alternaria toxins in the European population. EFSA J 14:4654–4686Google Scholar
  12. Escriva L, Oueslati S, Font G, Manyes L (2017) Alternaria mycotoxins in food and feed: an overview. J Food Qual 2017:1569748Google Scholar
  13. Estiarte N, Crespo-Sempere A, Marin S, Sanchis V, Ramos AJ (2018) Occurrence of Alternaria mycotoxins and quantification of viable Alternaria spp. during the food processing of tomato products in Spain. World Mycotoxin J 11:625–633CrossRefGoogle Scholar
  14. Fernandez-Blanco C, Font G, Ruiz MJ (2016) Role of quercetin on Caco-2 cells against cytotoxic effects of alternariol and alternariol monomethyl ether. Food Chem Toxicol 89:60–66CrossRefPubMedGoogle Scholar
  15. Fliszar-Nyul E, Lemli B, Kunsagi-Mate S, Dellafiora L, Dall’Asta C, Cruciani G, Petho G, Poor M (2019) Interaction of mycotoxin alternariol with serum albumin. Int J Mol Sci 20:e2352CrossRefPubMedGoogle Scholar
  16. Frizzell C, Ndossi D, Kalavou S, Eriksen GS, Verhaegen S, Sorlie M, Elliott CT, Ropstad E, Connolly L (2013) An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol. Toxicol Appl Pharmacol 271:64–71CrossRefPubMedGoogle Scholar
  17. Gambacorta L, Magista D, Perrone G, Murgolo S, Logrieco AF, Solfrizzol M (2018) Co-occurrence of toxigenic moulds, aflatoxins, ochratoxin A, Fusarium and Alternaria mycotoxins in fresh sweet peppers (Capsicum annuum) and their processed products. World Mycotoxin J 11:159–173CrossRefGoogle Scholar
  18. Gotthardt M, Asam S, Gunkel K, Moghaddam AF, Baumann E, Kietz R, Rychlik M (2016) Quantitation of six Alternaria toxins in infant foods applying stable isotope labelled standards. Front Microbiol 10:109CrossRefGoogle Scholar
  19. Griffin GF, Chu FS (1983) Toxicity of the Alternaria metabolites alternariol, alternariol methyl ether, altenuene, and tenuazonic acid in the chicken embryo assay. Appl Environ Microbiol 46:1420–1422PubMedPubMedCentralGoogle Scholar
  20. Hessel-Pras S, Kieshauer J, Roenn G, Luckert C, Braeuning A, Lampen A (2019) In vitro characterization of hepatic toxicity of Alternaria toxins. Mycotoxin Res 35(157):168Google Scholar
  21. Hickert S, Bergmann M, Ersen S, Cramer B, Humpf HU (2016) Survey of Alternaria toxin contamination in food from the German market, using a rapid HPLC-MS/MS approach. Mycotoxin Res 32:7–18CrossRefPubMedGoogle Scholar
  22. Hickert S, Hermes L, Marques LMM, Focke C, Cramer B, Lopes NP, Flett B, Humpf HU (2017) Alternaria toxins in south African sunflower seeds: cooperative study. Mycotoxin Res 33:309–321CrossRefPubMedGoogle Scholar
  23. Janic Hajnal E, Mastilovic J, Bagi F, Orcic D, Budakov D, Kos J, Savic Z (2019) Effect of wheat milling process on the distribution of Alternaria toxins. Toxins 11:139CrossRefPubMedCentralGoogle Scholar
  24. Mariani G, Bellver J (2018) Proteomics and metabolomics studies and clinical outcomes. Reproductomics 1:147–170CrossRefGoogle Scholar
  25. Oh J, Kim S, Cho K, Kim M, Suh C, Lee J, Kim KP (2017) Proteomic analysis of human follicular fluid in poor ovarian responders during in vitro fertilization. Proteomics 17:1600333CrossRefGoogle Scholar
  26. Pollock GA, DiSabatino CE, Heimsch RC, Hilbelink DR (1982) The subchronic toxicity and teratogenicity of alternariol monomethyl ether produced by Alternaria solani. Food Chem Toxicol 20:899–902CrossRefPubMedGoogle Scholar
  27. Puntscher H, Hankele S, Tillmann K, Attakpah E, Braun D, Kütt ML, Del Favero G, Aichinger G, Pahlke G, Höger H, Marko D, Warth B (2019) First insights into Alternaria multi-toxin in vivo metabolism. Toxicol Lett 301:168–178CrossRefPubMedGoogle Scholar
  28. Revelli A, Delle Piane L, Casano S, Molinari E, Massobrio M, Rinaudo P (2009) Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod Biol Endocrinol 7:40CrossRefPubMedPubMedCentralGoogle Scholar
  29. Santos RR, Schoevers EJ, Roelen BAJ, Fink-Gremmels J (2013) Mycotoxins and female reproduction: in vitro approaches. World Mycotoxin J 6:245–253CrossRefGoogle Scholar
  30. Santos RR, Schoevers EJ, Roelen BAJ (2014) Usefulness of bovine and porcine IVM/IVF models for reproductive toxicology. Reprod Biol Endocrinol 12:117CrossRefPubMedPubMedCentralGoogle Scholar
  31. Santos RR, Schoevers EJ, Wu X, Roelen BAJ, Fink-Gremmels J (2015) The protective effect of follicular fluid against the emerging mycotoxins alternariol and beauvericin. World Mycotoxin J 8:445–450CrossRefGoogle Scholar
  32. Sarkanj B, Ezekiel CN, Turner PC, Abia WA, Rychlik M, Krska R, Sulyok M, Warth B (2018) Ultra-sensitive, stable isotope assisted quantification of multiple urinary mycotoxin exposure biomarkers. Anal Chim Acta 1019:84–92CrossRefPubMedGoogle Scholar
  33. Schoevers E, Kidson A, Verheijden JH, Bevers M (2003) Effect of follicle-stimulating hormone on nuclear and cytoplasmic maturation of sow oocytes in vitro. Theriogenology 59:2017–2028CrossRefPubMedGoogle Scholar
  34. Schoevers EJ, Santos RR, Colenbrander B, Fink-Gremmels J, Roelen BA (2012) Transgenerational toxicity of zearalenone in pigs. Reprod Toxicol 34:110–119CrossRefPubMedGoogle Scholar
  35. Schoevers EJ, Santos RR, Fink-Gremmels J, Roelen BA (2016) Toxicity of beauvericin on porcine oocyte maturation and preimplantation embryo development. Reprod Toxicol 65:159–169CrossRefPubMedGoogle Scholar
  36. Schuchardt S, Ziemann C, Hansen T (2014) Combined toxicokinetic and in vivo genotoxicity study on Alternaria toxins. EFSA Supporting Publications 11:679.  https://doi.org/10.2903/sp.efsa.2014.EN-679
  37. Seli E, Robert C, Sirard M (2010) OMICS in assisted reproduction: possibilities and pitfalls. Mol Hum Reprod 16:513–530CrossRefPubMedGoogle Scholar
  38. Solhaug A, Eriksen GS, Holme JA (2016a) Mechanisms of action and toxicity of the mycotoxin alternariol: a review. Basic Clin Pharmacol Toxicol 119:533–539CrossRefPubMedGoogle Scholar
  39. Solhaug A, Karlsoen LM, Holme JA, Kristoffersen AB, Eriksen GS (2016b) Immunomodulatory effects of individual and combined mycotoxins in the THP-1 cell line. Toxicol in Vitro 36:120–132CrossRefPubMedGoogle Scholar
  40. Somfai T, Ozawa M, Noguchi J, Kaneko H, Ohnuma K, Karja NWK, Fahrudin M, Maedomari N, Dinnyes A, Nagai T, Kikuchi K (2006) Diploid porcine parthenotes produced by inhibition of first polar body extrusion during in vitro maturation of follicular oocytes. Reproduction 132:559–570CrossRefPubMedGoogle Scholar
  41. Stankiewicz T (2015) Biochemical composition of the fluid of ovarian cysts and pre-ovulatory follicles compared to the serum in sows. Tierarzti Prax Ausg G Grosstiere Nutztiere 43:216–221CrossRefGoogle Scholar
  42. Takeo S, Kimura K, Shirasuna K, Kuwayama T, Iwata H (2017) Age-associated deterioration in follicular fluid induces a decline in bovine oocyte quality. Reprod Fertil Dev 29:759–767CrossRefPubMedGoogle Scholar
  43. Tiemann U, Tomek W, Schneider F, Müller M, Pöhland R, Vanselow J (2009) The mycotoxins alternariol and alternariol methyl ether negatively affect progesterone synthesis in porcine granulosa cells in vitro. Toxicol Lett 186:139–145CrossRefPubMedGoogle Scholar
  44. Tiessen C, Fehr M, Schwarz C, Baechler S, Domnanich K, Bottler U, Pahlke G, Marko D (2013) Modulation of the cellular redox status by the Alternaria toxins alternariol and alternariol monomethyl ether. Toxicol Lett 216:23–30CrossRefPubMedGoogle Scholar
  45. Tiessen C, Ellmer D, Mikula H, Pahlke G, Warth B, Gehrke H, Zimmermann K, Heiss E, Frohlich J, Marko D (2017) Impact of phase I metabolism on uptake, oxidative stress and genotoxicity of the emerging mycotoxin alternariol and its monomethyl ether in esophageal cells. Arch Toxicol 91:1213–1226CrossRefPubMedGoogle Scholar
  46. Topi C, Tavcar-Kalcher G, Pavsic-Vrtac K, Babic J, Jakovac-Strain B (2019) Alternaria mycotoxins in grains from Albania: alternariol, alternariol monomethyl ether, tenuazonic acid and tentoxin. World Mycotoxin J 12:89–99CrossRefGoogle Scholar
  47. Van Wagtendonk-de Leeuw AM, Mullaart E, de Roos AP, Merton JS, den Daas JH, Kemp B, de Ruigh L (2000) Effects of different reproduction techniques: AI MOET or IVP, on health and welfare of bovine offspring. Theriogenology 53:575–597CrossRefGoogle Scholar
  48. Vatzias G, Hagen DR (1999) Effects of porcine follicular fluid and oviduct-conditioned media on maturation and fertilization of porcine oocytes in vitro. Biol Reprod 60:42–48CrossRefPubMedGoogle Scholar
  49. Vejdovszky K, Schmidt V, Warth B, Marko D (2017) Combinatory estrogenic effects between the isoflavones genistein and the mycotoxins zearalenone and alternariol in vitro. Mol Nutr Food Res 61:1CrossRefGoogle Scholar

Copyright information

© Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Farm Animal Health, Faculty of Veterinary MedicineUtrecht UniversityUtrechtThe Netherlands
  2. 2.Schothorst Feed ResearchLelystadThe Netherlands

Personalised recommendations