Skip to main content

Advertisement

SpringerLink
Log in

Alternariol disturbs oocyte maturation and preimplantation development

  • Original Article
  • Published:
Mycotoxin Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abeydeera L, Day B (1997) In vitro penetration of pig oocytes in a modified Tris-buffered medium: effect of BSA, caffeine and calcium. Theriogenology 48:537–544

    CAS  PubMed  Google Scholar 

  • 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 61:2

    Google Scholar 

  • 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 62:1483–1497

    PubMed  Google Scholar 

  • 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 19:797–803

    CAS  PubMed  Google Scholar 

  • 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 412:79–88

    CAS  PubMed  Google Scholar 

  • 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 25:149–157

    CAS  PubMed  Google Scholar 

  • 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 9:4554–4565

    CAS  PubMed  Google Scholar 

  • 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 9:639–643

    CAS  PubMed  Google Scholar 

  • 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 101:667–673

    CAS  PubMed  Google Scholar 

  • 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 130:199–206

    CAS  PubMed  Google Scholar 

  • 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 14:4654–4686

    Google Scholar 

  • Escriva L, Oueslati S, Font G, Manyes L (2017) Alternaria mycotoxins in food and feed: an overview. J Food Qual 2017:1569748

    Google Scholar 

  • 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 11:625–633

    CAS  Google Scholar 

  • 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 89:60–66

    CAS  PubMed  Google Scholar 

  • 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:e2352

    PubMed  Google Scholar 

  • 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 271:64–71

    CAS  PubMed  Google Scholar 

  • 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 11:159–173

    CAS  Google Scholar 

  • 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 10:109

    Google Scholar 

  • 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 46:1420–1422

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):168

    Google Scholar 

  • 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 32:7–18

    CAS  PubMed  Google Scholar 

  • 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 33:309–321

    CAS  PubMed  Google Scholar 

  • 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 11:139

    PubMed Central  Google Scholar 

  • Mariani G, Bellver J (2018) Proteomics and metabolomics studies and clinical outcomes. Reproductomics 1:147–170

    Google Scholar 

  • 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 17:1600333

    Google Scholar 

  • 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 20:899–902

    CAS  PubMed  Google Scholar 

  • 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 301:168–178

    CAS  PubMed  Google Scholar 

  • 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 7:40

    PubMed  PubMed Central  Google Scholar 

  • Santos RR, Schoevers EJ, Roelen BAJ, Fink-Gremmels J (2013) Mycotoxins and female reproduction: in vitro approaches. World Mycotoxin J 6:245–253

    CAS  Google Scholar 

  • Santos RR, Schoevers EJ, Roelen BAJ (2014) Usefulness of bovine and porcine IVM/IVF models for reproductive toxicology. Reprod Biol Endocrinol 12:117

    PubMed  PubMed Central  Google Scholar 

  • 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 8:445–450

    CAS  Google Scholar 

  • 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 1019:84–92

    CAS  PubMed  Google Scholar 

  • 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 59:2017–2028

    CAS  PubMed  Google Scholar 

  • Schoevers EJ, Santos RR, Colenbrander B, Fink-Gremmels J, Roelen BA (2012) Transgenerational toxicity of zearalenone in pigs. Reprod Toxicol 34:110–119

    CAS  PubMed  Google Scholar 

  • Schoevers EJ, Santos RR, Fink-Gremmels J, Roelen BA (2016) Toxicity of beauvericin on porcine oocyte maturation and preimplantation embryo development. Reprod Toxicol 65:159–169

    CAS  PubMed  Google Scholar 

  • 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

  • Seli E, Robert C, Sirard M (2010) OMICS in assisted reproduction: possibilities and pitfalls. Mol Hum Reprod 16:513–530

    CAS  PubMed  Google Scholar 

  • Solhaug A, Eriksen GS, Holme JA (2016a) Mechanisms of action and toxicity of the mycotoxin alternariol: a review. Basic Clin Pharmacol Toxicol 119:533–539

    CAS  PubMed  Google Scholar 

  • 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 36:120–132

    CAS  PubMed  Google Scholar 

  • 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 132:559–570

    CAS  PubMed  Google Scholar 

  • 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 43:216–221

    CAS  Google Scholar 

  • 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 29:759–767

    PubMed  Google Scholar 

  • 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 186:139–145

    CAS  PubMed  Google Scholar 

  • 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 216:23–30

    CAS  PubMed  Google Scholar 

  • 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 91:1213–1226

    CAS  PubMed  Google Scholar 

  • 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 12:89–99

    CAS  Google Scholar 

  • 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 53:575–597

    Google Scholar 

  • 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 60:42–48

    CAS  PubMed  Google Scholar 

  • 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 61:1

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands

    Eric J. Schoevers & Bernard A. J. Roelen

  2. Schothorst Feed Research, PO Box 533, 8200 AM, Lelystad, The Netherlands

    Regiane R. Santos

Authors
  1. Eric J. Schoevers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Regiane R. Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard A. J. Roelen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Regiane R. Santos.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Eric J. Schoevers passed way before publication of this work was completed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schoevers, E.J., Santos, R.R. & Roelen, B.A.J. Alternariol disturbs oocyte maturation and preimplantation development. Mycotoxin Res 36, 93–101 (2020). https://doi.org/10.1007/s12550-019-00372-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12550-019-00372-w

Keywords

Search

Navigation