FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Reprod Biol Endocrinol / Influence of mycotoxin zearalenone and its derivatives (alph...
Reproductive biology and endocrinology : RB&E2006; 4; 62; doi: 10.1186/1477-7827-4-62

Influence of mycotoxin zearalenone and its derivatives (alpha and beta zearalenol) on apoptosis and proliferation of cultured granulosa cells from equine ovaries.

Abstract: The mycotoxin zearalenone (ZEA) and its derivatives, alpha and beta-zearalenol (alpha and beta-ZOL), synthesized by genera Fusarium, often occur as contaminants in cereal grains and animal feeds. The importance of ZEA on reproductive disorders is well known in domestic animals species, particularly in swine and cattle. In the horse, limited data are available to date on the influence of dietary exposure to ZEA on reproductive health and on its in vitro effects on reproductive cells. The aim of this study was to evaluate the effects of ZEA and its derivatives, alpha and beta-ZOL, on granulosa cells (GCs) from the ovaries of cycling mares. Methods: The cell proliferation was evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test after 3 days exposure at different concentrations of ZEA and its derivatives (from 1 x 10-7 to 0.1 microM). The apoptosis induction was evaluated after 1 day exposure, by DNA analysis using flow cytometry. Results: An increase in cell proliferation with respect to the control was observed in the presence of ZEA at 1 x 10-3 and 1 x 10-4 microM and apoptosis was induced by all mycotoxins at different concentrations. Conclusions: The simultaneous presence of apoptosis and proliferation in GC cultures treated with zearalenones could indicate that these mycotoxins could be effective in inducing follicular atresia. These effects of zearalenones may result from both direct interaction with oestrogen-receptors as well as interaction with the enzymes 3alpha (beta)-hydroxysteroid dehydrogenase (HSD), involved in the synthesis and metabolism of endogenous steroid hormones. These cellular disturbances, described for the first time in equine GCs cultured in vitro, could be hypothesized as referred to reproductive failures of unknown ethiology in the mare.
Get Full Text
Publication Date: 2006-11-30 PubMed ID: 17137489PubMed Central: PMC1697814DOI: 10.1186/1477-7827-4-62Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigated the impact of a mycotoxin called zearalenone (ZEA) and its derivatives on the cell growth and mortality in the ovaries of horses. The mycotoxin was found to boost proliferation and accelerate cell death (apoptosis), which could potentially lead to reproductive issues.

Mycotoxins and Their Effects

  • Zearalenone (ZEA) and its derivatives, alpha and beta-zearalenol (alpha and beta-ZOL), are mycotoxins synthesized by the Fusarium genus. These contaminants are found in cereal grains and animal feeds.
  • ZEA’s impact on reproductive issues has been extensively studied in animals like swine and cattle, but little data is available on its effects on horses.

Objectives

  • This study investigates the effects of ZEA and its derivatives on ovarian granulosa cells (GCs) in horses, primarily focusing on cell proliferation and apoptosis.

Methods

  • Cell proliferation was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test after exposing the cells to various concentrations of ZEA and its derivatives for three days.
  • A DNA analysis using flow cytometry was conducted to determine apoptosis induction after a one-day exposure.

Results

  • ZEA at concentrations of 1 x 10-3 and 1 x 10-4 microM stimulated cell proliferation above control levels.
  • All mycotoxins induced apoptosis at different concentrations.

Conclusions

  • The concurrent increase in cell proliferation and apoptosis in cultures treated with zearalenones suggests that these mycotoxins could induce follicular atresia, a condition that leads to the degradation of ovarian follicles.
  • Zearalenones’ effects might arise from direct interaction with estrogen receptors and the enzymes 3alpha (beta)-hydroxysteroid dehydrogenase (HSD), which participate in the synthesis and metabolism of endogenous steroid hormones.
  • The results, being the first of this nature in equine granulosa cells cultured in vitro, hint towards an association with the unexplained reproductive failures in horses.

Cite This Article

APA
Minervini F, Giannoccaro A, Fornelli F, Dell'Aquila ME, Minoia P, Visconti A. (2006). Influence of mycotoxin zearalenone and its derivatives (alpha and beta zearalenol) on apoptosis and proliferation of cultured granulosa cells from equine ovaries. Reprod Biol Endocrinol, 4, 62. https://doi.org/10.1186/1477-7827-4-62

Publication

Reproductive biology and endocrinology : RB&E
ISSN: 1477-7827
NlmUniqueID: 101153627
Country: England
Language: English
Volume: 4
Pages: 62

Researcher Affiliations

Minervini, Fiorenza
  • Institute of Sciences of Food Production (ISPA), National Research Council (CNR), Via Amendola 122/O, 70124 Bari, Italy. fiorenza.minervini@ispa.cnr.it
Giannoccaro, Alessandra
    Fornelli, Francesca
      Dell'Aquila, Maria Elena
        Minoia, Paolo
          Visconti, Angelo

            MeSH Terms

            • Animal Feed
            • Animals
            • Apoptosis / drug effects
            • Cell Division / drug effects
            • Cells, Cultured
            • DNA / metabolism
            • Estrogens, Non-Steroidal / pharmacology
            • Female
            • Flow Cytometry
            • Follicular Atresia / drug effects
            • Food Contamination
            • Granulosa Cells / cytology
            • Granulosa Cells / drug effects
            • Horses
            • Zearalenone / pharmacology
            • Zeranol / analogs & derivatives
            • Zeranol / pharmacology

            References

            This article includes 46 references
            1. Placinta CM, D'Mello JPF, Mac Donald AMC. A review of worldwide contamination of cereal grains and animal feed with Fusarium micotoxins. Anim Feed Sci Tech 1999;78:21–37.
              doi: 10.1016/S0377-8401(98)00278-8google scholar: lookup
            2. Olsen M, Pettersson H, Sandholm K, Visconti A, Kiessling KH. Metabolism of zearalenone by sow intestinal mucosa in vitro.. Food Chem Toxicol 1987 Sep;25(9):681-3.
              doi: 10.1016/0278-6915(87)90101-3pubmed: 2958396google scholar: lookup
            3. Olsen M. Metabolism of zearalenone in farm animals. 1989. pp. 167–177.
            4. Malekinejad H, Maas-Bakker R, Fink-Gremmels J. Species differences in the hepatic biotransformation of zearalenone.. Vet J 2006 Jul;172(1):96-102.
              doi: 10.1016/j.tvjl.2005.03.004pubmed: 15907386google scholar: lookup
            5. Katzenellenbogen BS, Katzenellenbogen JA, Mordecai D. Zearalenones: characterization of the estrogenic potencies and receptor interactions of a series of fungal beta-resorcylic acid lactones.. Endocrinology 1979 Jul;105(1):33-40.
              pubmed: 446414doi: 10.1210/endo-105-1-33google scholar: lookup
            6. Haschek WM, Haliburton JC. Fusarium moniliforme and zearalenone toxicoses in domestic animals. 1896. pp. 213–235.
            7. Osweiler GD. Occurrence and clinical manifestations of trichothecene toxicoses and zearalenone toxicoses. 1986. pp. 31–42.
            8. Diekman MA, Green ML. Mycotoxins and reproduction in domestic livestock.. J Anim Sci 1992 May;70(5):1615-27.
              pubmed: 1388147doi: 10.2527/1992.7051615xgoogle scholar: lookup
            9. Gaumy JL, Bailly JD, Benard G, Guerre P. Zèaralénone: origine et effets chez les animaux d'élevage. Revue Méd Vét 2001;152:123–136.
            10. Obremski K, Gajecki M, Zwierzchowski W, Zielonka L, Otrocka-Domagała I, Rotkiewicz T, Mikołajczyk A, Gajecka M, Polak M. Influence of zearalenone on reproductive system cell proliferation in gilts.. Pol J Vet Sci 2003;6(4):239-45.
              pubmed: 14703867
            11. Gimeno A, Quintavilla JA. Analytical and mycotoxicological study of a natural outbreak of zearalenone mycotoxicosis in horse. Proceeding of International Symposium on Mycotoxins, National Research Centre: Cairo (Egypt) 1983. pp. 387–392.
            12. Raymond SL, Smith TK, Swamy HV. Effects of feeding a blend of grains naturally contaminated with Fusarium mycotoxins on feed intake, serum chemistry, and hematology of horses, and the efficacy of a polymeric glucomannan mycotoxin adsorbent.. J Anim Sci 2003 Sep;81(9):2123-30.
              pubmed: 12968685doi: 10.2527/2003.8192123xgoogle scholar: lookup
            13. Raymond SL, Smith TK, Swamy HV. Effects of feeding a blend of grains naturally contaminated with Fusarium mycotoxins on feed intake, metabolism, and indices of athletic performance of exercised horses.. J Anim Sci 2005 Jun;83(6):1267-73.
              pubmed: 15890804doi: 10.2527/2005.8361267xgoogle scholar: lookup
            14. Juhász J, Nagy P, Kulcsár M, Szigeti G, Reiczigel J, Huszenicza G. Effect of low-dose zearalenone exposure on luteal function, follicular activity and uterine oedema in cycling mares.. Acta Vet Hung 2001;49(2):211-22.
              doi: 10.1556/AVet.49.2001.2.11pubmed: 11402650google scholar: lookup
            15. Hochsteiner W, Schuh M. [Occurrence of the fusariotoxins deoxynivalenol and zearalenone in Austrian feedstuff in the period from 1995 to 1999].. Dtsch Tierarztl Wochenschr 2001 Jan;108(1):19-23.
              pubmed: 11232419
            16. Cecconi S, Ciccarelli C, Barberi M, Macchiarelli G, Canipari R. Granulosa cell-oocyte interactions.. Eur J Obstet Gynecol Reprod Biol 2004 Jul 1;115 Suppl 1:S19-22.
              doi: 10.1016/j.ejogrb.2004.01.010pubmed: 15196711google scholar: lookup
            17. Lacey M, Bohday J, Fonseka SM, Ullah AI, Whitehead SA. Dose-response effects of phytoestrogens on the activity and expression of 3beta-hydroxysteroid dehydrogenase and aromatase in human granulosa-luteal cells.. J Steroid Biochem Mol Biol 2005 Aug;96(3-4):279-86.
              doi: 10.1016/j.jsbmb.2005.03.006pubmed: 16023337google scholar: lookup
            18. Hsueh AJ, Billig H, Tsafriri A. Ovarian follicle atresia: a hormonally controlled apoptotic process.. Endocr Rev 1994 Dec;15(6):707-24.
              doi: 10.1210/er.15.6.707pubmed: 7705278google scholar: lookup
            19. Guthrie HD, Welch GR, Cooper BS, Zakaria AD, Johnson LA. Flow cytometric determination of degraded deoxyribonucleic acid in granulosa cells to identify atretic follicles during preovulatory maturation in the pig.. Biol Reprod 1994 Jun;50(6):1303-11.
              doi: 10.1095/biolreprod50.6.1303pubmed: 8080917google scholar: lookup
            20. Blondin P, Dufour M, Sirard MA. Analysis of atresia in bovine follicles using different methods: flow cytometry, enzyme-linked immunosorbent assay, and classic histology.. Biol Reprod 1996 Mar;54(3):631-7.
              doi: 10.1095/biolreprod54.3.631pubmed: 8835385google scholar: lookup
            21. Rosales-Torres AM, Avalos-Rodríguez A, Vergara-Onofre M, Hernández-Pérez O, Ballesteros LM, García-Macedo R, Ortíz-Navarrete V, Rosado A. Multiparametric study of atresia in ewe antral follicles: histology, flow cytometry, internucleosomal DNA fragmentation, and lysosomal enzyme activities in granulosa cells and follicular fluid.. Mol Reprod Dev 2000 Mar;55(3):270-81.
              doi: 10.1002/(SICI)1098-2795(200003)55:3<270::AID-MRD5>3.0.CO;2-Hpubmed: 10657046google scholar: lookup
            22. Tajima K, Orisaka M, Hosokawa K, Amsterdam A, Kotsuji F. Effects of ovarian theca cells on apoptosis and proliferation of granulosa cells: changes during bovine follicular maturation.. Biol Reprod 2002 Jun;66(6):1635-9.
              doi: 10.1095/biolreprod66.6.1635pubmed: 12021041google scholar: lookup
            23. Tsafriri A, Braw RH. Experimental approaches to atresia in mammals.. Oxf Rev Reprod Biol 1984;6:226-65.
              pubmed: 6099538
            24. Hinrichs K, Schmidt AL, Friedman PP, Selgrath JP, Martin MG. In vitro maturation of horse oocytes: characterization of chromatin configuration using fluorescence microscopy.. Biol Reprod 1993 Feb;48(2):363-70.
              doi: 10.1095/biolreprod48.2.363pubmed: 8439626google scholar: lookup
            25. Davidson TR, Chamberlain CS, Bridges TS, Spicer LJ. Effect of follicle size on in vitro production of steroids and insulin-like growth factor (IGF)-I, IGF-II, and the IGF-binding proteins by equine ovarian granulosa cells.. Biol Reprod 2002 Jun;66(6):1640-8.
              doi: 10.1095/biolreprod66.6.1640pubmed: 12021042google scholar: lookup
            26. Skorska-Wyszyńska E, Jakimiuk E, Gajecka M, Młynarczuk J, Obremski K, Gajecki M. Preliminary evaluation of influence of zearalenone on cocultures of granulosa and internal theca cells of ovarian follicles in bitches in in vitro culture.. Pol J Vet Sci 2004;7(4):305-9.
              pubmed: 15633791
            27. Minervini F, Fornelli F, Flynn KM. Toxicity and apoptosis induced by the mycotoxins nivalenol, deoxynivalenol and fumonisin B1 in a human erythroleukemia cell line.. Toxicol In Vitro 2004 Feb;18(1):21-8.
              doi: 10.1016/S0887-2333(03)00130-9pubmed: 14630058google scholar: lookup
            28. Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K. Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones.. Biochem J 2000 Oct 1;351(Pt 1):67-77.
              doi: 10.1042/0264-6021:3510067pmc: PMC1221336pubmed: 10998348google scholar: lookup
            29. Malekinejad H, Van Tol HT, Colenbrander B, Fink-Gremmels J. Expression of 3alpha- and 3beta-hydroxy steroid dehydrogenase mRNA in COCs and granulosa cells determines Zearalenone biotransformation.. Toxicol In Vitro 2006 Jun;20(4):458-63.
              doi: 10.1016/j.tiv.2005.09.007pubmed: 16246520google scholar: lookup
            30. Takahashi M, Iwata N, Hara S, Mukai T, Takayama M, Endo T. Cyclic change in 3 alpha-hydroxysteroid dehydrogenase in rat ovary during the estrous cycle.. Biol Reprod 1995 Dec;53(6):1265-70.
              doi: 10.1095/biolreprod53.6.1265pubmed: 8562680google scholar: lookup
            31. Pedersen HG, Watson ED, Telfer EE. Effect of ovary holding temperature and time on equine granulosa cell apoptosis, oocyte chromatin configuration and cumulus morphology.. Theriogenology 2004 Aug;62(3-4):468-80.
              doi: 10.1016/j.theriogenology.2003.10.006pubmed: 15226003google scholar: lookup
            32. Pedersen HG, Watson ED, Telfer EE. Apoptosis in equine granulosa cells and its relationship to cumulus expansion and oocyte chromatin configuration in ovarian follicles.. J Reprod Fertil Suppl 2000;(56):455-62.
              pubmed: 20681158
            33. Quirk SM, Cowan RG, Harman RM, Hu CL, Porter DA. Ovarian follicular growth and atresia: the relationship between cell proliferation and survival.. J Anim Sci 2004;82 E-Suppl:E40-52.
              pubmed: 15471814doi: 10.2527/2004.8213_supple40xgoogle scholar: lookup
            34. Quirk SM, Cowan RG, Harman RM. The susceptibility of granulosa cells to apoptosis is influenced by oestradiol and the cell cycle.. J Endocrinol 2006 Jun;189(3):441-53.
              doi: 10.1677/joe.1.06549pubmed: 16731776google scholar: lookup
            35. Hay MR, Cran DG, Moor RM. Structural changes occurring during atresia in sheep ovarian follicles.. Cell Tissue Res 1976 Jul 6;169(4):515-29.
              pubmed: 991198doi: 10.1007/bf00218150google scholar: lookup
            36. Yang MY, Rajamahendran R. Morphological and biochemical identification of apoptosis in small, medium, and large bovine follicles and the effects of follicle-stimulating hormone and insulin-like growth factor-I on spontaneous apoptosis in cultured bovine granulosa cells.. Biol Reprod 2000 May;62(5):1209-17.
              doi: 10.1095/biolreprod62.5.1209pubmed: 10775168google scholar: lookup
            37. Okolski A, Bézard J, Magistrini M, Palmer E. Maturation of oocytes from normal and atretic equine ovarian follicles as affected by steroid concentrations.. J Reprod Fertil Suppl 1991;44:385-92.
              pubmed: 1795282
            38. Albrizio M, Dell'Aquila ME, Aiudi G, Cinone M, Lacalandra GM, Minoia P. Analysis of apoptosis in mural granulosa cells in the mare. Proceeding 3rd National Congress of Biotechnologies 1–3 July 1999. Consorzio Interuniversitario Biotecnologie. Urbino (Italy); 1999. p. 33.
            39. Dell'Aquila ME, Albrizio M, Maritato F, Minoia P, Hinrichs K. Meiotic competence of equine oocytes and pronucleus formation after intracytoplasmic sperm injection (ICSI) as related to granulosa cell apoptosis.. Biol Reprod 2003 Jun;68(6):2065-72.
              doi: 10.1095/biolreprod.102.009852pubmed: 12606481google scholar: lookup
            40. Pedersen HG, Watson ED, Telfer EE. Analysis of atresia in equine follicles using histology, fresh granulosa cell morphology and detection of DNA fragmentation.. Reproduction 2003 Mar;125(3):417-23.
              doi: 10.1530/rep.0.1250417pubmed: 12611605google scholar: lookup
            41. Powell DG, Troppman A, Tobin T. Mare Reproductive Loss Syndrome and Associated Syndromes: Toxicological Hypotheses. Proceedings of the First Workshop on Mare Reproductive Loss Syndrome Section V, University of Kentuki; 2003. pp. 59–75.
            42. Newman K. Review of mycotoxins as a possible cause of mare reproductive loss syndrome. Proceedings of the First Workshop on Mare Reproductive Loss Syndrome Section V, University of Kentuki; 2003. pp. 66–68.
            43. Newman KE, Raymond SL. Effects of mycotoxins in horses. The mycotoxin blue book Nottingham University Press; 2005. pp. 57–76.
            44. Alm H, Brüssow KP, Torner H, Vanselow J, Tomek W, Dänicke S, Tiemann U. Influence of Fusarium-toxin contaminated feed on initial quality and meiotic competence of gilt oocytes.. Reprod Toxicol 2006 Jul;22(1):44-50.
              doi: 10.1016/j.reprotox.2005.11.008pubmed: 16431077google scholar: lookup
            45. Tiemann U, Tomek W, Schneider F, Vanselow J. Effects of the mycotoxins alpha- and beta-zearalenol on regulation of progesterone synthesis in cultured granulosa cells from porcine ovaries.. Reprod Toxicol 2003 Nov-Dec;17(6):673-81.
              doi: 10.1016/j.reprotox.2003.07.001pubmed: 14613819google scholar: lookup
            46. Minervini F, Dell'Aquila ME, Maritato F, Minoia P, Visconti A. Toxic effects of the mycotoxin zearalenone and its derivatives on in vitro maturation of bovine oocytes and 17 beta-estradiol levels in mural granulosa cell cultures.. Toxicol In Vitro 2001 Aug-Oct;15(4-5):489-95.
              doi: 10.1016/S0887-2333(01)00068-6pubmed: 11566582google scholar: lookup

            Citations

            This article has been cited 12 times.
            1. Widodo OS, Etoh M, Kokushi E, Uno S, Yamato O, Pambudi D, Okawa H, Taniguchi M, Lamid M, Takagi M. Practical Application of Urinary Zearalenone Monitoring System for Feed Hygiene Management of a Japanese Black Cattle Breeding Herd-The Relationship between Monthly Anti-Müllerian Hormone and Serum Amyloid A Concentrations.. Toxins (Basel) 2022 Feb 16;14(2).
              doi: 10.3390/toxins14020143pubmed: 35202171google scholar: lookup
            2. Song JL, Zhang GL. Deoxynivalenol and Zearalenone: Different Mycotoxins with Different Toxic Effects in the Sertoli Cells of Equus asinus.. Cells 2021 Jul 27;10(8).
              doi: 10.3390/cells10081898pubmed: 34440667google scholar: lookup
            3. Kinkade CW, Rivera-Núñez Z, Gorcyzca L, Aleksunes LM, Barrett ES. Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review.. Toxins (Basel) 2021 May 24;13(6).
              doi: 10.3390/toxins13060373pubmed: 34073731google scholar: lookup
            4. Ropejko K, Twarużek M. Zearalenone and Its Metabolites-General Overview, Occurrence, and Toxicity.. Toxins (Basel) 2021 Jan 6;13(1).
              doi: 10.3390/toxins13010035pubmed: 33418872google scholar: lookup
            5. Marin DE, Pistol GC, Bulgaru CV, Taranu I. Cytotoxic and inflammatory effects of individual and combined exposure of HepG2 cells to zearalenone and its metabolites.. Naunyn Schmiedebergs Arch Pharmacol 2019 Aug;392(8):937-947.
              doi: 10.1007/s00210-019-01644-zpubmed: 30919009google scholar: lookup
            6. Zhang GL, Feng YL, Song JL, Zhou XS. Zearalenone: A Mycotoxin With Different Toxic Effect in Domestic and Laboratory Animals' Granulosa Cells.. Front Genet 2018;9:667.
              doi: 10.3389/fgene.2018.00667pubmed: 30619484google scholar: lookup
            7. Zhang GL, Song JL, Ji CL, Feng YL, Yu J, Nyachoti CM, Yang GS. Zearalenone Exposure Enhanced the Expression of Tumorigenesis Genes in Donkey Granulosa Cells via the PTEN/PI3K/AKT Signaling Pathway.. Front Genet 2018;9:293.
              doi: 10.3389/fgene.2018.00293pubmed: 30108608google scholar: lookup
            8. Lu Y, Zhang Y, Liu JQ, Zou P, Jia L, Su YT, Sun YR, Sun SC. Comparison of the toxic effects of different mycotoxins on porcine and mouse oocyte meiosis.. PeerJ 2018;6:e5111.
              doi: 10.7717/peerj.5111pubmed: 29942714google scholar: lookup
            9. Bertero A, Moretti A, Spicer LJ, Caloni F. Fusarium Molds and Mycotoxins: Potential Species-Specific Effects.. Toxins (Basel) 2018 Jun 15;10(6).
              doi: 10.3390/toxins10060244pubmed: 29914090google scholar: lookup
            10. Ben Salem I, Boussabbeh M, Helali S, Abid-Essefi S, Bacha H. Protective effect of Crocin against zearalenone-induced oxidative stress in liver and kidney of Balb/c mice.. Environ Sci Pollut Res Int 2015 Dec;22(23):19069-76.
              doi: 10.1007/s11356-015-5086-2pubmed: 26233739google scholar: lookup
            11. Li Y, Zhang B, He X, Cheng WH, Xu W, Luo Y, Liang R, Luo H, Huang K. Analysis of individual and combined effects of ochratoxin A and zearalenone on HepG2 and KK-1 cells with mathematical models.. Toxins (Basel) 2014 Mar 26;6(4):1177-92.
              doi: 10.3390/toxins6041177pubmed: 24674935google scholar: lookup
            12. Minervini F, Dell'Aquila ME. Zearalenone and reproductive function in farm animals.. Int J Mol Sci 2008 Dec;9(12):2570-2584.
              doi: 10.3390/ijms9122570pubmed: 19330093google scholar: lookup
            Subscribe to our newsletter
            Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.