INTRODUCTION Zearalenone is a natural mycotoxin produ - PDF document

terior, associated withÊconsumption ofÊmoldy food.Zearalenone Ê metabolismÊin the bodyÊoccursÊ in the liver,through twoÊdifferent pathways. First, theÊ conjugateÊ with., 1967). Although:1197-202, 2012.Effect of Zearalenone Administrated at Late Gestation Days onFertility of The F-1 Offspring in Swiss webster (Mus musculusEfecto de la Zearalenona Administrada los D’as Finales de Gestaci—n sobrela Fertilidad de las Cr’as F-1 en Ratones Swiss Webster (Yulia IrnidayantiIRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012.SUMMARY: ZearalenoneÊsolution was given to dams miceÊsubcutaneouslyÊat a dose ofÊ30 mg/kg body weightÊat the age ofÊpregnancyÊweanedÊonÊ 21 days of age. The liveÊ birthÊ indexÊ andÊviability of the F-1 offspring were recorded. Determination of fertilitoffspring were undertaken by mating interlitters. On days 18 of gestation, the F-1 offspring were killed by cervical dislocation. The observationn loss. Theas the result of mating between control male with treated female and treatedÊ male with tretaed female of the F-1 offspring. It could beconcluded that in the F-1 offspring, zearalenone interfered the process of ovarian develoment, stimulated the differentation of the uterus,decreased the fertility of the female and the effect of zearalenon was more persistent in the female than in the maleKEY WORDS: Zearalenone; Fertilitas indeks; Gestation indeks; Number of implantation; Persistent.Biology Department, Jakarta State of University, Faculty of Mathematic and Science, Indonesia. Gestation days (GD)Dose Zearalenone(mg/kg bw)Numberof damsWeight bodyof dams at GD-0(g) X SemWeight bodyof dams at GD-18(g) X SemAdded of body weightin dams at GD-18(g) X Sem01026.18 0.4444.04 1.2918.17 0.6613 s/d 18301027.86 0.5946.07 1.3518.21 0.96 Gestation days(GD)DoseZearalenone(mg/kg bb)Numberof damsAverage of fetus live Sem (total)Live birth Indeks SemA/B x 100%Number of implantationAverage X Sem (total)13 s/d 180108.60 0.60 (86)88.07 4.259.80 0.53 (98)30106.50 1.13 (65)67.41 11.049.90 0.59 (99) etÊal.grow on grain stored in a state of very highÊhumidity. Corn,growth. Therefore, when the feed consumed by livestockmay affect the differentiation and development of the fetalthen do research to find out whether zearalenone affect theMATERIAL AND METHODmusculus) Swiss Webster derived from laboratory animalkept in cages, Department of Biology, ITB. Male and femalemice were kept in separate cages. Each virgin female micethat were in a state of estrus, aged 11-12 weeks with bodyat 17.00. The existence of vaginal plug the next morning isa sign of copulation and indicates at gestation day zero. ThenZearalenone used in this study, derived from Makordissolved in sesame oil. Zearalenone solution injected daily,subcutaneously in mice at gestation 13 to 18 days. TheToÊcalculate theÊperinatalÊmortalityÊindexÊis theÊnumber of livingÊin theÊPN-4 divided byÊthe number ofpupsÊlivingÊin theÊPN-0Êmultiplied byÊ100% (WeilÊ1972). Determination of fertility of the F-1 offspring wereundertaken by mating interlitter.MatingÊ patterns consisted KÊ X K, II. KÊ XÊ P, III.Ê P XÊ K, IV.Ê PÊ XÊ P. Each groupÊconsists of 10Ê matingÊpairsÊof mice.ÊAt the age ofÊ18 days ofÊpregnancy, all F-1generation miceÊwere killedÊ byÊ cervicalÊ dislocation,Ê andthenÊcalculatedÊthe number ofÊfemalesÊthat were pregnant. The"Wilcoxon'sÊrankÊsum test" is usedÊto computeÊnon-andÊfertilityÊindex ÊusedÊtestingÊ"ChiÊSquare" (Zar,Ê1984).RESULTS AND DISCUSSIONweightÊare listedÊin Table I. AverageÊ body weightTable I. The body weight of mice dams (Swiss Webster) administrated zearalenone at a dose of 30 mg/kg body weight atTable II. The condition of F-1 offspring from the dams, who was administrated zearalenone with a dose of 30 mg/kg body weightIRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. Average of fetus live PN-0 Sem(total) PN-1 Sem(total) PN-4 Sem(total) PN-21 Sem(total) Total of fetus birth-dead at PN-0 Sem(total) Perinatal mortality Êindex Sem(total)F/A+F x 100 Viability Index PN-4 Sem(total )C/A x 100 WeaningÊindex at PN-21 Sem(total)E/D x 100 % 13 s/d 0.60(86) 1.13(82) 7.70 0.97 5.90 0.10 0.10 0.10(1) 1.11 1.11 89.03 8.79 98.33 1.67 1.13(65) 1.13(65) 6.10 1.18 6.00 0.00 1.80 1.03(18) 20.34 1.21 93.65 6.35 100.00 0.00 Table III. Viability Index, perinatalmortality index and weaning index of F-1 offspring in mice from dams were administrated zeandÊincrease ofÊ body weightÊdid not differÊfrom the controlÊ treatment.weight. Average number of puppies bornÊin the treated groupÊtendencytoÊdecrease Therefore, live birthÊ index alsoÊtendency to be lower thanwith controls (Table II).ÊThis is causedÊby aÊnumber ofÊ stillborn pupsÊismortalityÊof miceÊat birth. This situation is supported by the research et al. (1969), ChangÊ et al. and Berger (1981), thatthe abilityÊof mice generationÊF-1 to live,Ê can be seenÊ in TableÊ III.WeaningÊindex and viability index on mice treatment fromÊF-1offspring,Ê althoughÊ higherÊ thanÊ controls,Ê butÊnot significantly.toÊPN-Ê21. Perinatal mortality index miceÊF-1 offspring, althoughÊÊstatisticallyÊnot significantly different from controls, but tendencyÊ toÊbehigher.ÊIt therefore seems zearalenone tendency causeÊthe death. and Berger zearalenone in female swine caused the death of pups atÊ birth. ThereforepregnantÊfemale mice (Collins). InÊ Table III, shows thatÊ the fertilitytrolÊ femalesÊwas 90,ÊwhichÊtendency to be higherÊthanÊthe control. WhileindexÊ is 80. ThisÊ conditionÊis causedÊby theÊmating test results,thereare 5Êand 4ÊmiceÊareÊnotÊpregnant.All mice areÊnotÊpregnant,afterÊsurgeryshowedÊ abnormalities inÊovarianÊandÊuterine dilatation. TheÊ resultsÊare consistentÊwith researchÊwas done by Weaver (1986), whichinÊvirginÊfemale pigs, orallyÊcauses decrease inÊconceptionÊrate.According toÊ Edgren & Clancy (1968) and Yasuda (1981),The fertility of F-1Êoffspring in miceÊ also supported by theÊgestationÊIRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. seemsÊzearalenoneÊ greater effectÊon fertilityÊof female mice,ÊsignificantÊdifferentÊfromÊthe controlÊ matingÊ pairsÊ test.can be concludedÊthat the effect of zearalenone was moreof mice generationÊF-1,Êare listedÊin Table V and Table VI.concludedÊ thatÊ zearalenone no effect on theÊnumberhigherÊthanÊcontrol group. The lowest ofÊimplantationstudyÊ concludedÊ thatÊzearalenone not affectÊovarianbutÊzearalenone affectÊ the function ofÊuterine ÊÊon F-1offspring of Ê mice,Ê whichÊ disruptÊ the ÊuterineÊenvironment,thus inhibiting implantation. This data supported by thethanÊ controlÊgroup. While the number ofÊdeadÊfetus, whichtreated andÊmalesÊÊtreatedÊ withÊfemales treatment,Êmoretal intrauterineÊdeath in F-1 offspring mice,ÊcausedÊby thehighÊ percentage of resorption embryos.ÊThis is different withpercentage of total intrauterine death in F-1 offspring dams,whrerever caused by fetus death. Thus it can beÊ concluded,Êmice, there is still a realÊeffect onÊfemale miceÊF-1ÊTable IV. Fertilityindexandgestationindex of F-1offspring mice fromdams were administrated zearalenone with adose of30 kg/kg body weightat gestation days 13 to 18.Table V.Percentageloss ofgestationF-1offspring fromdams were administrated zearalenone with a dose of30 kg/kgbody weightat gestation days 13 to 18.IRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. From the results ofresearch has beendonetoday,itcan be concludedthat zearalenone is nottoxic to thedamsof mice, tendency tocausethe death ofthe F-1generationmiceat birth,does notaffect the abilityof micelivingF-1offspring throughPN-21.Zearalenonecauses decreasedfertility of female mice generation F-1,isembryo toxictomice F-2offspring andits effect on female miceofgenerationF-1is more persistent than male mice,sothatreproduction isimpaired.The author wishes to thank Prof. Dr. Sri Sudarwatiand Dr. Lien A. Sutasurya for helpful comments on theIRNIDAYANTI, Y. Swiss Webster (:1197-1202, 2012. Se administr— una soluci—n subcut‡nea de zearalenona en una dosis de 30 mg/kg de peso corporal en ratonaspre–adas entre 13 a 18 d’as de gestaci—n. Los ratones control recibieron s—lo aceite de sŽsamo. Adem‡s, a las ratonas pre–adas PALABRAS CLAVE: Zearalenona; Indice de Fertilidad; Indice de gestaci—n; Nœmero de implantaci—n; Persistencia.Table VI. Performance of reproduction of F-1offspring mice fromdams were administrated zearalenone with a doseof30 kg/kg body weightat gestation days 13 to 18. Bannett, G. A. & Shotwell, O. L. Zearalenone in cereal J. Am. Oil Chem. Soc., 56(9)Berger, T.; Esbenshade, K. L.; Diekman, M. A.; Hoagland, T. &Tuite, J. Influence of prepubertal consumption of zearalenoneJ. Anim. Sci., 53(6)Chang, K.; Kurtz, H. J. & Mirocha, C. J. Effects of the mycotoxinAm. J. Vet. Res.,Collins, T. F. X. Multigeneration reproduction studies. In:Handbook of teratology. Wilson, J. G. & Fraser, F. C. (Eds.).Vol 4. New York-London, Plenum Press, 1977. pp.205-7.IRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. Edgren, R. A. & Clancy, D. P. The effects of norgestrel, ethinylrats treated during pregnancy. Int. J. Fertil., 13(3)Katzenellenbogen, B. S.; Katzenellenbogen, J. A. & Mordecai, D.Endocrinology, 105(1)rat liver. Acta Pharmacol. Toxicol. (Copenh.), 43(4)Am. J. Vet. Res., 30(4)Manson, J. & Kang, Y. Test methods for assessing femalereproductive and developmental toxicity. In: Hayes, A. (Ed.).Principles and Method of Toxicology. New York, Raven Press,Appl. Microbiol., 15(3)Mirocha, C. J.; Pathre, S. V.; Schauerhamer, B. & Christensen, C.M. Natural occurrence of Fusarium toxins in feedstuff. Environ. Microbiol., 32(4)Ueno, Y.; Shimada, N.; Yagasaki, S. & Enomoto, M. Toxicologicalapproaches to the metabolites of Fusaria. VII. Effects of(Tokyo), 22(12)Weil, C. S.; Woodside, M. D.; Carpenter, C. P. & Smith, H. F. Jr.teratogenic effect. Toxicol. Appl. Pharmacol., 21Weaver, G. A.; Kurtz, H. J.; Behrens, J. C.; Robison, T. S.; Seguin,B. E.; Bates, F. Y. & Mirocha, C. J. Effect of zearalenone onthe fertility of virgin dairy heifers. Am. J. Vet. Res., 47(6)Yasuda, Y.; Kihara, T. & Nishimura, H. Effect of ethinyl estradiolTeratology, 23(2)Zar, H. J. New Jersey, Prentice Hall Inc.,Yulia IrnidayantiIRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. terior, associated withÊconsumption ofÊmoldy food.Zearalenone Ê metabolismÊin the bodyÊoccursÊ in the liver,through twoÊdifferent pathways. First, theÊ conjugateÊ with., 1967). Although:1197-Effect of Zearalenone Administrated at Late Gestation Days onFertility of The F-1 Offspring in Swiss webster (Efecto de la Zearalenona Administrada los D’as Finales de Gestaci—n sobrela Fertilidad de las Cr’as F-1 en Ratones Swiss Webster (Yulia IrnidayantiIRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012.SUMMARY:13 to 18 days.ÊControl miceÊwere given only sesameÊoil. Furthermore,Ê damsÊmice wereÊ allowed toÊdeliver their litter and pups wereÊweanedÊonÊ 21 days of age. The liveÊ birthÊ indexÊ andÊviability of the F-1 offspring were recorded. Determination of fertility of the F-1offspring were undertaken by mating interlitters. On days 18 of gestation, the F-1 offspring were killed by cervical dislocation. The observationwas performed on the number of live or dead fetus, embryo resorption, the number of implantation and the percentage of gestation loss. Theresult revealed that administration of zearalenone on days 13 to 18 of gestation caused a significant decreasein the number of implantationas the result of mating between control male with treated female and treatedÊ male with tretaed female of the F-1 offspring. It could beconcluded that in the F-1 offspring, zearalenone interfered the process of ovarian develoment, stimulated the differentation of the uterus,decreased the fertility of the female and the effect of zearalenon was more persistent in the female than in the maleKEY WORDS: Zearalenone; Fertilitas indeks; Gestation indeks; Number of implantation; Persistent.Biology Department, Jakarta State of University, Faculty of Mathematic and Science, Indonesia. 1198 Gestation days (GD)Dose Zearalenone(mg/kg bw)Numberof damsWeight bodyof dams at GD-0(g) X SemWeight bodyof dams at GD-18(g) X SemAdded of body weightin dams at GD-18(g) X 01026.18 0.4444.04 1.2918.17 0.6613 s/d 181027.86 0.5946.07 1.3518.21 0.96 Gestation days(GD)DoseZearalenone(mg/kg bb)Numberof damsAverage of fetus live Sem (total)Live birth Indeks SemA/B x 100%Number of implantationAverage X Sem (total)13 s/d 18108.60 0.60 (86)88.07 9.80 0.53 (98)106.50 1.13 (65)67.41 11.049.90 0.59 (99) grow on grain stored in a state of very highÊhumidity. Corn,growth. Therefore, when the feed consumed by livestockmay affect the differentiation and development of the fetalthen do research to find out whether zearalenone affect theMATERIAL AND METHODmusculus) Swiss Webster derived from laboratory animalkept in cages, Department of Biology, ITB. Male and femalemice were kept in separate cages. Each virgin female micethat were in a state of estrus, aged 11-12 weeks with bodyat 17.00. The existence of vaginal plug the next morning isa sign of copulation and indicates at gestation day zero. ThenZearalenone used in this study, derived from Makordissolved in sesame oil. Zearalenone solution injected daily,subcutaneously in mice at gestation 13 to 18 days. TheToÊcalculate theÊperinatalÊmortalityÊindexÊis theÊnumber ofpupsÊlivingÊin theÊPN-0Êmultiplied byÊ100% (WeilÊ1972). Determination of fertility of the F-1 offspring wereundertaken by mating interlitter.MatingÊ patterns consisted KÊ X K, II. KÊ XÊ P, III.Ê P XÊ K, IV.Ê PÊ XÊ P. Each groupÊconsists of 10Ê matingÊpairsÊof mice.ÊAt the age ofÊ18 days ofÊpregnancy, all F-1thenÊcalculatedÊthe number ofÊfemalesÊthat were pregnant. The"Wilcoxon'sÊrankÊsum test" is usedÊto computeÊnon-andÊfertilityÊindex ÊusedÊtestingÊ"ChiÊSquare" (Zar,Ê1984).RESULTS AND DISCUSSIONweightÊare listedÊin Table I. AverageÊ body weightTable I. The body weight of mice dams (Swiss Webster) administrated zearalenone at a dose of 30 mg/kg body weight atTable II. The condition of F-1 offspring from the dams, who was administrated zearalenone with a dose of 30 mg/kg body weightIRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. 1199 Average of fetus live PN-0(total) PN-1 Sem(total) PN-4 Sem(total) PN-21 Sem(total) Total of fetus birth-dead at PN-0 Sem(total) Perinatal mortality Êindex(total)F/A+F x 100 Viability Index PN-4 Sem(total )C/A x 100 WeaningÊindex at PN-21(total)E/D x 100 % 13 s/d 0 10 (86) (82) 7.70 0.97 5.90 0.10 0.10 0.10(1) 1.11 1.11 89.03 98.33 1.67 30 10 (65) (65) 6.10 1.18 6.00 0.00 1.80 1.03(18) 20.34 1.21 93.65 100.00 0.00 Table III. Viability Index, perinatalmortality index and weaning index of F-1 offspring in mice from dams were administrated zearalenone with a dose of 30 kg/andÊincrease ofÊ body weightÊdid not differÊfrom the controlÊ treatment.weight. Average number of puppies bornÊin the treated groupÊtendencytoÊdecrease Therefore, live birthÊ index alsoÊtendency to be lower thanwith controls (Table II).ÊThis is causedÊby aÊnumber ofÊ stillborn pupsÊismortalityÊof miceÊat birth. This situation is supported by the research. and Berger the abilityÊof mice generationÊF-1 to live,Ê can be seenÊ in TableÊ III.WeaningÊindex and viability index on mice treatment fromÊF-1offspring,Ê althoughÊ higherÊ thanÊ controls,Ê butÊnot significantly.toÊPN-Ê21. Perinatal mortality index miceÊF-1 offspring, althoughÊÊstatisticallyÊnot significantly different from controls, but tendencyÊ toÊbehigher.ÊIt therefore seems zearalenone tendency causeÊthe death. and Berger zearalenone in female swine caused the death of pups atÊ birth. ThereforepregnantÊfemale mice (Collins). InÊ Table III, shows thatÊ the fertilitytrolÊ femalesÊwas 90,ÊwhichÊtendency to be higherÊthanÊthe control. WhileindexÊ is 80. ThisÊ conditionÊis causedÊby theÊmating test results,thereare 5Êand 4ÊmiceÊareÊnotÊpregnant.All mice areÊnotÊpregnant,afterÊsurgeryshowedÊ abnormalities inÊovarianÊandÊuterine dilatation. TheÊ resultsÊare consistentÊwith researchÊwas done by Weaver inÊvirginÊfemale pigs, orallyÊcauses decrease inÊconceptionÊrate.According toÊ Edgren & Clancy (1968) and Yasuda The fertility of F-1Êoffspring in miceÊ also supported by theÊgestationÊIRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. 1200 seemsÊzearalenoneÊ greater effectÊon fertilityÊof female mice,ÊsignificantÊdifferentÊfromÊthe controlÊ matingÊ pairsÊ test.can be concludedÊthat the effect of zearalenone was moreof mice generationÊF-1,Êare listedÊin Table V and Table VI.concludedÊ thatÊ zearalenone no effect on theÊnumberhigherÊthanÊcontrol group. The lowest ofÊimplantationstudyÊ concludedÊ thatÊzearalenone not affectÊovarianbutÊzearalenone affectÊ the function ofÊuterine ÊÊon F-1offspring of Ê mice,Ê whichÊ disruptÊ the ÊuterineÊenvironment,thus inhibiting implantation. This data supported by thethanÊ controlÊgroup. While the number ofÊdeadÊfetus, whichtal intrauterineÊdeath in F-1 offspring mice,ÊcausedÊby thehighÊ percentage of resorption embryos.ÊThis is different withpercentage of total intrauterine death in F-1 offspring dams,whrerever caused by fetus death. Thus it can beÊ concluded,Êmice, there is still a realÊeffect onÊfemale miceÊF-1ÊTable IV. Fertilityindexandgestationindex of F-1offspring mice fromdams were administrated zearalenone with adose of30 kg/kg body weightat gestation days 13 to 18.Table V.Percentageloss ofgestationF-1offspring fromdams were administrated zearalenone with a dose of30 kg/kgbody weightat gestation days 13 to 18.IRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. 1201 From the results ofresearch has beendonetoday,itcan be concludedthat zearalenone is nottoxic to thedamsof mice, tendency tocausethe death ofthe F-1generationmiceat birth,does notaffect the abilityof micelivingF-1offspring throughPN-21.Zearalenonecauses decreasedfertility of female mice generation F-1,isembryo toxictomice F-2offspring andits effect on female miceofgenerationF-1is more persistent than male mice,sothatreproduction isimpaired.The author wishes to thank Prof. Dr. Sri Sudarwatiand Dr. Lien A. Sutasurya for helpful comments on theIRNIDAYANTI, Y. Swiss Webster (:1197-1202, 2012.pre–adas entre 13 a 18 d’as de gestaci—n. Los ratones control recibieron s—lo aceite de sŽsamo. Adem‡s, a las ratonas pre–adas se lespermiti— amamantar a sus cr’as para ser destetadas a los 21 d’as de edad. El ’ndice de nacidos vivos y viabilidad de la descendencia F-1fuer registrado. La determinaci—n de la fertilidad de la descendencia F-1 se llev— a cabo por apareamiento intercr’as. El d’a 18 degestaci—n, la descendencia F-1 se sacrific— por dislocaci—n cervical. Se observ— el nœmero de fetos vivos y muertos, reabsorci—n delembri—n, nœmero de implantaciones y porcentaje de pŽrdida de gestaci—n. El resultado revel— que la administraci—n de la zearalenonaentre los d’as 13-18 de gestaci—n caus— un significativo descenso en el nœmero de implantaciones, como resultado del apareamiento entremachos controles con hembras tratadas y machos tratados con hembras tratadas (F-1 cr’as). Se puede concluir que en la descendencia F-1, la zearalenona interfiere en el proceso de desarrollo ov‡rico, estimulado la diferenciaci—n del œtero, disminuyendo la fertilidad de laPALABRAS CLAVE: Zearalenona; Indice de Fertilidad; Indice de gestaci—n; Nœmero de implantaci—n; Persistencia.Table VI. Performance of reproduction of F-1offspring mice fromdams were administrated zearalenone with a doseof30 kg/kg body weightat gestation days 13 to 18. Bannett, G. A. & Shotwell, O. L. Zearalenone in cereal J. Am. Oil Chem. Soc., 56(9)Berger, T.; Esbenshade, K. L.; Diekman, M. A.; Hoagland, T. &Tuite, J. Influence of prepubertal consumption of zearalenoneJ. Anim. Sci., 53(6)Chang, K.; Kurtz, H. J. & Mirocha, C. J. Effects of the mycotoxinAm. J. Vet. Res.,Collins, T. F. X. Multigeneration reproduction studies. In:Handbook of teratology. Wilson, J. G. & Fraser, F. C. (Eds.).Vol 4. New York-London, Plenum Press, 1977. pp.205-7.IRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012. Edgren, R. A. & Clancy, D. P. The effects of norgestrel, ethinylrats treated during pregnancy.Katzenellenbogen, B. S.; Katzenellenbogen, J. A. & Mordecai, D.Endocrinology, 105(1)rat liver. Acta Pharmacol. Toxicol. (Copenh.), 43(4)Am. J. Vet. Res., 30(4)Manson, J. & Kang, Y. Test methods for assessing femalereproductive and developmental toxicity. In: Hayes, A. (Ed.).Principles and Method of Toxicology. New York, Raven Press,Appl. Microbiol., 15(3)Mirocha, C. J.; Pathre, S. V.; Schauerhamer, B. & Christensen, C.M. Natural occurrence of Fusarium toxins in feedstuff. Environ. Microbiol., 32(4)Ueno, Y.; Shimada, N.; Yagasaki, S. & Enomoto, M. Toxicologicalapproaches to the metabolites of Fusaria. VII. Effects of(Tokyo), 22(12)Weil, C. S.; Woodside, M. D.; Carpenter, C. P. & Smith, H. F. Jr.teratogenic effect. Toxicol. Appl. Pharmacol., 21Weaver, G. A.; Kurtz, H. J.; Behrens, J. C.; Robison, T. S.; Seguin,B. E.; Bates, F. Y. & Mirocha, C. J. Effect of zearalenone onthe fertility of virgin dairy heifers. Am. J. Vet. Res., 47(6)Yasuda, Y.; Kihara, T. & Nishimura, H. Effect of ethinyl estradiolTeratology, 23(2)Zar, H. J. New Jersey, Prentice Hall Inc.,Yulia IrnidayantiIRNIDAYANTI, Y. Effect of zearalenone administrated at late gestation days on fertility of the F-1 offspring in Swiss webster (:1197-1202, 2012.