Ochratoxin A: Developmental and reproductive toxicity-an overview

Birth Defects Research Part B - Developmental and Reproductive Toxicology

Volumn 98, Issue 6, 2013, Pages 493-502

  Malir, Frantisek ^a   Ostry, Vladimir ^b   Pfohl Leszkowicz, Annie ^c   Novotna, Eva ^d  

^a UNIVERSITY OF HRADEC KRALOVE   (Czech Republic)

^b NATIONAL INSTITUTE OF PUBLIC HEALTH   (Czech Republic)

^c Ecole Nationale Superieure d'Architecture de Toulouse   (France)

^d Charles University in Prague Faculty of Pharmacy   (Czech Republic)

Author keywords

Developmental toxicity; Ochratoxin A; Pregnant woman; Reprotoxicity; Teratogenicity; Testicular cancer

Indexed keywords

OCHRATOXIN;

ARTICLE; CONGENITAL DISORDER; DEVELOPMENTAL TOXICITY; FETUS DEATH; FETUS MALFORMATION; FETUS RESORPTION; HUMAN; NONHUMAN; PLACENTA; PRIORITY JOURNAL; REPRODUCTIVE TOXICITY; TERATOGENICITY; TESTIS CANCER;

ANIMALIA; CRICETINAE; PHASIANIDAE; RATTUS;

DEVELOPMENTAL TOXICITY; OCHRATOXIN A; PREGNANT WOMAN; REPROTOXICITY; TERATOGENICITY; TESTICULAR CANCER;

ANIMALS; CALCIUM CHANNEL BLOCKERS; CARCINOGENS; CRICETINAE; ENDOCRINE DISRUPTORS; ENVIRONMENTAL EXPOSURE; FEMALE; HUMANS; MALE; MICE; OCHRATOXINS; PREGNANCY; RATS; REPRODUCTION; SPERMATOZOA; TERATOGENESIS; TERATOGENS; TESTICULAR NEOPLASMS;

EID: 84892953664     PISSN: 15429733     EISSN: 15429741     Source Type: Journal    
DOI: 10.1002/bdrb.21091     Document Type: Article

References (157)

1. Abdel-Wahhab MA, Nada SA, Arbid MS. 1999. Ochratoxicosis: prevention of developmental toxicity by L-methionone in rats. J Appl Toxicol 19:7-12.
2. Acampora D, Avantaggiato V, Tuorto F, Simeone A. 1997. Genetic control of brain morphogenesis through Otx gene dosage requirement. Development 124:3639-3650.
3. Andonova IE, Sarueva RB, Horvath AD, Simeonov VA, Dimitrov PS, Petropoulos EA, Ganev VS. 2004. Balkan endemic nephropathy and genetic variants of glutathione S-transferases. J Nephrol 17:390-398.
4. Anonymous. 2013. NIEHS. Last reviewed, June 05, 2013. Endocrine Disruptors. Available at: www.niehs.nih.gov/health/topics/agents/endocrine/.
5. 14C- labelled ochratoxin A in pregnant mice. Food Chem Toxicol 21:563-568.
6. 1 and ochratoxin A in pregnant mice. Food Chem Toxicol 21:563-568.
7. Arora RG. 1982. Mycotoxin induced effects on the prenatal development in mice: a teratopathologic and autoradiographic study of aflatoxin B1, ochratoxin A and zearalenone. Ph.D. thesis, Swedish University of Agricultural Sciences, Uppsala, Sweden.
8. Arora RG, Froelein H, Fellner-Feldegg H. 1983. Inhibition of ochratoxin A teratogenesis by zearalenone and diethylstilboestrol. Fundament Chem Toxicol 21:779-783.
9. Azpilicueta CA, Arbeloa MI, de Maquirriain PFJ. 2008. Natural and syntethic occurring forms of the ochratoxins. In: Papadopoulos KN, editor. Food chemistry research developments. New York: Nova Science Publishers; 116p.
10. Ballinger MB, Phillips TD, Kubena LF. 1986. Assessment of the distribution and elimination of ochratoxin A in the pregnant rat. J Food Safety 8:11-24.
11. Behrman RE. 1996. Nelson texbook of pediatrics. 15th ed. Philadelphia: VB Saunders. p 448-451.
12. Biasucci G, Calabrese G, Di Giuseppe R, Carrara G, Colombo F, Mandelli B, Maj M, Bertuzzi T, Pietri A, Rossi F. 2011. The presence of ochratoxin A in cord serum and in human milk and its correspondence with maternal dietary habits. Eur J Nutr 50:211-218.
13. Biró K, Barna-Vetró I, Pécsi T, Szabó E, Winkler G, Fink-Gremmels J, Solti L. 2003. Evaluation of spermatological parameters in ochratoxin A-challenged boars. Theriogenol 60:199-207.
14. Bonassi S, Neri M, Puntoni R. 2001. Validation of biomarkers as early predictors of disease. Mutat Res 480-481:349-358.
15. Bose S, Sinha SP. 1994. Modulation of ochratoxin - produced genotoxicity in mice by vitamin C. Food Chem Toxicol 32:533-537.
16. Bouaziz C, Sharaf el dein O, Martel C, Golli EE, Abid-Essefi S, Brenner C, Lemaire C, Bacha H. 2011. Molecular events involved in ochratoxin A induced mitochondrial pathway of apoptosis, modulation by Bcl-2 family members. Environ Toxicol 26:579-590.
17. Breitholtz-Emanuelsson A, Olsen M, Oskarsson A, Palminger I, Hult K. 1993. Ochratoxin A in cow's milk and in human milk with corresponding human blood samples. J AOAC Int 76:842-846.
18. Brown MH, Szczek GM, Purmalis BP. 1976. Teratogenic and toxic effets of ochratoxin A in rats. Toxicol Appl Pharmacol 37:331-338.
19. Castegnaro M, Mohr U, Pfohl-Leszkowicz A, Esteve J, Steinmann J, Tillmann T, Michelon, J, Bartsch H. 1998. Sex- and strain-specific induction of renal tumors by ochratoxin A in rats correlates with DNA adduction. Inter J Cancer 77:70-75.
20. Castegnaro M, Canadas D, Vrabcheva T, Petkova-Bocharova T, Chernozemsky IN, Pfohl-Leszkowicz A. 2006. Balkan endemic nephropathy: role of ochratoxins A through biomarkers. Mol Nutr Food Res 50:519-529.
21. Chakraborty D, Verma R. 2009. Spermatotoxic effect of ochratoxin and its amelioration by Emblica officinalis aqueous extract. Act Pol Pharm Drug Res 66:689-695.
22. Chu FS. 1971. Interaction of ochratoxin A with bovine serum albumine. Arch Biochem Biophys 147:359-366.
23. Chu FS. 1974. A comparative study of the interaction of ochratoxins with bovine serum albumine. Biochem Pharmacol 23:1105-1107.
24. Dai J, Park G, Perry JL, Ill'ichev YV, Bow DAJ, Pritchard JB, Faucet V, Pfohl-Leszkowicz A, Manderville R, Simon JD. 2004. Molecular aspects of the transport and toxicity of ochratoxin A. Acc Chem Res 37:874-881.
25. Degen GH, Mayer S, Blaszkevicz M. 2007. Biomonitoring of ochratoxin A in grain workers. Mycotoxin Res 23:88-93.
26. Di Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. 1997. Pharmacotherapy: a pathophysiological approach. 3rd ed. Stamford, CT: Appleton Lauge. p 1564-1584.
27. Duarte SC, Lino CM, Pena A. 2011. Ochratoxin A in feed of food-producing animals: an undesirable mycotoxin with health and performance effects. Vet Microbiol 154:1-13.
28. Dwivedi P. 1984. The immunological and pathological changes in poultry induced by ochratoxin A. Ph.D. thesis, University of Edinburgh, UK.
29. El Adlouni C, Pinelli E, Azémar B, Zaoui D, Beaune P, Pfohl-Leszkowicz A. 2000. Role of CYP 2C and microsomal glutathione-S-transferase in modulating susceptibility to ochratoxin A genotoxicity. Environ Mol Mut 35:123-131.
30. Ewald C, Heer, A. 1989. The sperm quality of 4 boars during the assimilation of mycotoxin-contaminated feed (ochratoxin A) and after changing feed-a case study. Berl Munch Tierarztl Wochenschr 102:261-266.
31. Farag IM, Abdel-Aziz KB, Nada SA, Tawfek NS, Farouk T, Darwish HR. 2010. Modulation of ochratoxin-induced oxidative stress, genotoxicity and spermatotoxic alterations by Lactobacillus rhamnosus GC in male Albino mice. J Am Sci 6:575-587.
32. Faucet-Marquis V, Pont F, Størmer FC, Rizk T, Castegnaro M, Pfohl-Leszkowicz A. 2006. Evidence of a new dechlorinated OTA derivative formed in opossum kidney cell cultures after pre-treatment by modulators of glutathione pathways. Correlation with DNA adducts formation. Mol Nutr Food Res 50:530-542.
33. Fenske M, Fink-Gremmels J. 1990. Effects of fungal metabolites on testosterone secretion in vitro. Arch Toxicol 64:72-75.
34. Frizzell C, Verhaegen S, Ropstad E, Elliott CT, Connally L. 2013. Endocrine disrupting effects of ochratoxin A at the level of nuclear receptor activation and steroigenesis. Toxicol Lett 217:243-250.
35. Fukui Y, Hoshino K, Kameyama Y, Yasui T, Toda C, Nagano H. 1987. Placental transfer of ochratoxin A and its cytotoxin effect on the mouseembryonic brain. Food Chem Toxicol 25:17-24.
36. Fukui Y, Hyasaka S, Itoh M, Takeuschi Y. 1992. Development of neurons and synapses in ochratoxin A-induced microcephalic mice: a quantitative assessment of somatosensory cortex. Neurotoxicol Teratol 14:191-196.
37. Gareis M, Märtlbauer E, Bauer J, Gedek B. 1988. Determination of ochratoxin A in human milk. Z Lebensm Unters Forsch 186:114-117.
38. Garel S, Huffman KJ, Rubenstein JLR. 2003. Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants. Development 130:1903-1914.
39. Gharbi A, Trillon O, Betbeder AM. 1993. Some efects of ochratoxin A, a mycotoxin contaminating feeds and food, on rat testis. Toxicol 83:9-18.
40. Gilani SH, Bancroft J, Reily M. 1978. Teratogenicity of ochratoxin A in chick embryos. Tox Appl Pharmacol 46:543-546.
41. Gilbert J, Brereton P, MacDonald S. 2001. Assessment of dietary exposure to ochratoxin A in the UK using a duplicate diet approach and analysis of urine and plasma samples. Food Addit Contam 18:1088-1093.
42. Gupta M, Bandyopadhyay S, Mazumdar SK, Paul B. 1980. Ovarian steroidogenesis in rats following ochratoxin A treatment. Toxicol Appl Pharmacol 53:515-520.
43. Hadjeba-Medjdoub K, Faucet-Marquis V, Monje MC, Dohnal V, Polisenska I, Pfohl-Leszkowicz A. 2013. Is mycotoxin-contaminated pet-food responsible of reduced fertility and stillbirth? Proceeding of 35th Mycotoxin Workshop, Ghent, Belgium, May 2013. 104p.
44. Hallen IP, Breitholtz-Emanuelsson A, Hult K, Olsen M, Oskarsson A. 1998. Placental and lactational transfer of ochratoxin A in rats. Nat Toxins 6:43-49.
45. Hansen DK, Abbot DB. 2009. Developmental toxicology. 3rd ed. New York: Informa Healthcare USA p 1-384.
46. 1, zearalenone and ochratoxin A on some hormones related to fertility in male rats. Life Sci J 7:64-72.
47. Hassan ZU, Khan MZ, Saleemi MK, Khan A, Javed I, Bhatti SA. 2012. Toxico-pathological effects of in ovo inoculation of ochratoxin A (OTA) in chick embryos and subsequently in hatched chicks. Toxicol Pathol 40:33-39.
48. Hayes AW, Hood RD, Lee HL. 1974. Teratogenic effects of ochratoxin A in mice. Teratology 9:93-98.
49. Hood RD, Naughton MJ, Hayes AW. 1975. Teratogenic effects of ochratoxin A in hamsters. Teratology 11:23 A (abst.).
50. Hood RD, Naughton MJ, Hayes AW. 1976. Prenatal effects of ochratoxin A in hamsters. Teratology 13, 11-14.
51. Hood RD, Kuczuk MH, Szczech GM. 1978. Effects in mice of simultaneous prenatal exposure to ochratoxin A and T-2 toxin. Teratology 17:25-30.
52. Hsuuw YD, Chan WH, Yu JS. 2013. Ochratoxin A inhibits mouse embryonic development by activating a mitochondrion-dependent apoptotic signaling pathway. Int J Mol Sci 14:935-953.
53. Huyghe E, Plante P, Thonneau PF. 2007. Testicular cancer variations in time and space in Europe. Eur Urol 51:621-628.
54. IARC. 1993. Monographs on the evaluation of carcinogenic risks to humans: Some naturally occuring substances: Food items and costituents, heterocyclic aromatic amines and mycotoxins. Lyon, France: IARC 56:523-524.
55. Jennings-Gee JE, Tozlovanu M, Manderville R, Miller MS, Pfohl-Leszkowicz A, Schwartz GG. 2010. Ochratoxin A: in utero exposure in mice induces adducts in testicular DNA. Toxins 2:1428-1444.
56. Jonsyn FE, Maxwell SM, Hendrickse RG. 1995. Human fetal exposure to ochratoxin A and aflatoxins. Ann Trop Paediatr 15:3-9.
57. Joosten HMLJ, Goetz J, Pittet A, Schellenberg M, Bucheli P. 2001. production of ochratoxin A by Aspergillus carbonarius on coffee cherries. Int J Food Microbiol 65:39-44.
58. Kacsoh, B. 2000. Endocrine physiology. New York, San Francisco, St.Louis, Auckland, Bogota, Caracas, London: The Mc Graw-Hill companies, Inc.
59. Katagiri R-I, Kurome M, Teshima Y, Ueta E, Naruse I. 2007. Prevention of ochratoxin A-induced neural tube defects by folic acid in the genetic polydactyly/arhinencephaly mouse, Pdn/Pdn. Congenit Anom 47:90-96.
60. Klapec T, Šarkanj B, Banjari I, Strelec I. 2012. Urinary ochtratoxin A and ochratoxin alpha in pregnant women. Food Chem Toxicol 50:4487-4492.
61. Knudsen LE, Hansen Å. 2007. Biomarkers of intermediate endpoints in environmental and occupational health. Int J Hyg Environ Health 210:461-470.
62. Knudsen TB. 1997. Cell death. In: Kavlock RJ, Daston GP, editors. Drug toxicity in embryonic development I. Vol 124. Berlin: Springer. p 211-244.
63. Kovacs F, Sandor G, Vanyi A, Domany S, Zomborsky-Kovacs M. 1995. Detection of ochratoxin A in human blood and colostrum. Acta Vet Hung 43:393-400.
64. Krentz A, Murphy MW, Kim S, Cook MS, Capel B, Zhu R, Matin A, Sarver AL, Parker KL, Griswold MD, Looijenga LHJ, Bardwell VJ, Zarkower D. 2009. The DM domain protein DMRT1 is a dose-sensitive regulator of fetal germ cell proliferation and pluripotency. Proc Natl Acad Sci USA 106:22323-22328.
65. Kuiper-Goodman T, Scott PM, Watanabe H. 1987. Risk assessment of the mycotoxin zearalenone. Regul Toxicol Pharmacol 7:253-306.
66. Kuiper-Goodman T, Hilts C, Billiard SM, Kiparissis Y, Richard IDK, Hayward S. 2010. Health risk assessment of ochratoxin A for all age-sex strata in a market economy. Food Addit Contam 27:212-240.
67. Kumar SN, Telang AG, Singh KP, Jain AK, Afroz M, Patil RD. 2011. Experimentally induced toxicity of ochratoxin A and endosulfan in male wistar rats: a hormonal disorder in adult male rats. J Anim Vet Adv 10(13):1750-1755.
68. Lalitha Kunjamma CR, Nair MK. 1997. Pathomorphology of the combined effects of ochratoxin A and citrinin in chicken embryos. Indian Vet J 74:22-25
69. Li S, Marquardt RR, Frohlich AA. 2000. Identification of ochratoxins and some of their metabolites in bile and urine of rats. Food Chem Toxicol 38:141-152.
70. Loebstein R, Koren G. 2002. Clinical relevance of therapeutic drug monitoring during pregnancy. Ther Drug Monit 24:15-22.
71. Malir F, Ostry V, Pfohl-Leszkowicz A, Roubal T. 2012. Ochratoxin A exposure biomarkers in the Czech Republic and comparison with foreign countries. Biomarkers 17:577-589.
72. Malir F, Ostry V, Novotna E. 2013a. Toxicity of the mycotoxin ochratoxin A in the light of recent data. Toxin Rev 32:19-33.
73. Malir F, Ostry V, Dofkova M, Roubal T, Dvorak V, Dohnal V. 2013b. Ochratoxin A levels in blood serum of Czech women in the first trimester of pregnancy and its correspondence with dietary intake of the mycotoxin contaminant. Biomarkers 18:673-678.
74. Mantle PG. 2010. Comments on "Ochratoxin A: In utero Exposure in Mice Induces Adducts in Testicular DNA. Toxins 2010, 2:1428-1444"-Mis-citation of rat literature to justify a hypothetical role for ochratoxin A in testicular cancer. Toxins 2:2333-2336.
75. Mantle PG, Nolan CC. 2010. Pathological outcomes in kidney and brain in male fischer rats given dietary ochratoxin A, commencing at one year of age. Toxins 2:1100-1110.
76. Marin-Kuan M, Nestler SW, Verguet C, Bezencon D, Piguet R, Mansourian R, Holzwarth J, Grigorov M, Delatour T, Mantle P, Cavin C, Schilter B. 2006. A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin A carcinogenicity in rat. Toxicol Sci 89:120-134.
77. Mayura K, Reddy RV, Hayes AW, Berndt WO. 1982. Embryocidal, fetotoxic and teratogenic effects of ochratoxin A in rats. Toxicology 25:175-185.
78. Mayura K, Hayes AW, Berndt WO. 1983. Effects of dietary protein on teratogenicity of ochratoxin A in rats. Toxicol 27:147-157.
79. Mayura K, Parker R, Berndt WO, Phillips TD. 1984a. Effects of simultaneous prenatal exposure to ochratoxin A and citrinin in the rat. J Toxicol Environ Health 13:553-561.
80. Mayura K, Stein AF, Berndt WO, Phillips TD. 1984b. Teratogenic effects in rats with impaired renal function. Toxicology 32:277-285.
81. Mayura K, Edwards JF, Maull EA, Phillips. 1989. The effects of ochratoxin A on postimplantation rat embryos in culture. Arch Environ Contam Toxicol 18:411-415.
82. Micco C, Ambruzzi MA, Miraglia M, Brera C, Onori R, Benelli L. 1991. Contamination of human milk with ochratoxin A. IARC Sci Publ 115:105-108.
83. Minervi F, Giannoccaro A, Nicassio M, Panzarini G, Lacalandra GM. 2013. First evidence of placental transfer of ochratoxin A in horses. Toxins 5:84-92.
84. Miraglia M, Brera C, Corneli S, Cava E. 1998. Occurrence of ochratoxin A (OTA) in maternal serum, placenta and funiculum. In: Miraglia M, van Egmond H, Brera C, Gilbert J, Eds. Proceed.of IX International IUPAC Symposium on Mycotoxins and Phycotoxins-Developments in Chemistry, Toxicology and Food Safety. Alaken Inc.: Fort Collins, Co, USA, pp. 165-179.
85. Monnet-Tschudi F, Sorg O, Honegger P, Zurich MG, Huggett AC, Schilter B. 1997. Effects of the naturaly occurring food mycotoxin ochratoxin A on brain cells in culture. Neurotoxicol 18:831-839.
86. Moré J, Camguilhem R. 1979. Efects of low doses of ochratoxin A after intratesticular injection in the rat. Experientia 35:890-892.
87. Moré J, Galtier P. 1974. Toxicité de l'ochratoxine A. I. Effet embryotoxique et teratogène chez le rat. Ann Rech Vet 5:167-178.
88. Moré J, Galtier P. 1975. Toxicité de l'ochratoxine A. II. Effets du traitement sur la descendance (F1 et F2) des rates intoxiquées. Ann Rech Vet 6:379-389.
89. Moré J, Galtier P. 1978a. Toxicité de l'ochratoxine A. III. Effets pendant les stades initiaux de la gestation Chez le rat. Ann Rech Vet 8:169-173.
90. Moré J, Galtier P. 1978b. Embryotoxic and teratogenic effects of OA in rats. In XIXth morphological congess symposia, Prague, Charles University. p 321-326.
91. Muñoz K, Campos V, Blaszkewicz M, Vega M, Alvarez A, Neira J, Degen GH. 2010. Exposure of neonates to ochratoxin A: first biomonitoring results in human milk (kolostrum) from Chile. Mycotoxin Res 26:59-67.
92. Murphy MW, Sarver AL, Rice D, Hatzi K, Ye K, Melnick A, Heckert LL, Zarkower D, Bardwell VJ. 2010. Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Double sex homolog DMRT1 in the juvenile testis. Proc Natl Acad Sci USA 107:13360-13365.
93. Myllynen P, Vähäkangas K. 2013. Placental transfer and metabolism: an overview of the experimental models utilizing human placental tissue. Toxicol In Vitro 27:507-512.
94. O'Brien E, Prietz A, Dietrich DR. 2005. Investigation of the teratogenic potential of ochratoxin A and B using the FETAX system. Birth Defects Res B Dev Reprod Toxicol 74:417-423.
95. Ostry, V., Malir, F., Ruprich, J. 2013. Producers and important dietary sources of ochratoxin A and citrinin. Toxins 5:1574-1586.
96. Patil RD, Dwivedi P, Sharma AK. 2006. Critical period and minimum single oral dose of ochratoxin A for inducing developmental toxicity in pregnant Wistar rats. Reprod Toxicol 22:679-687.
97. Pelis RM, Hartman RC, Wright SH, Wunz TM, Groves CE. 2007. Influence of estrogen and xenoestrogens on basolateral uptake of tetraethylammonium by opossum kidney cells in culture. J Pharmacol Exp Ther 323:555-561.
98. Petkova-Bocharova T, Pfohl-Leszkowicz A, Hadjiolov D, Spirov K. 1998a. Investigation on the genotoxicity of ochratoxin A by measurement of DNA-adducts in different organs of Syrian hamsters. Rev Med Vet 149:658.
99. Petkova-Bocharova T, Stoichev II, Chernozemsky IN, Castegnaro M, Pfohl-Leszkowicz A. 1998b. Formation of DNA adducts in tissues of mice progeny through transplacental contamination and/or lactation after administration of a single dose of ochratoxin A to pregnant mother. Environ Molecular Mutagen 32:155-162.
100. Pfohl-Leszkowicz A. 2008. Formation, persistence and significance of DNA adduct formation in relation to some pollutants from a broad perspective. Adv Mol Toxicol 2:183-239.
101. Pfohl-Leszkowicz A. 2009. Ochratoxin A and aristolochic acid involvement in nephropathies and associated urothelial tract tumours. Arh Hig Rada Toksikol 60:465-483.
102. Pfohl-Leszkowicz A. 2013. Evaluation de risques liés à l'exposition, en milieu professionnel et environnemental, aux mycotoxines. Bulletin de veille scientifique ANSES, N° 22.
103. Pfohl-Leszkowicz A, Manderville RA. 2007. Ochratoxin A: an overview on toxicity and carcinogenicity in animals and humans. Mol Nutr Food Res 51:61-99.
104. Pfohl-Leszkowicz A, Manderville RA. 2012. An update on direct genotoxicity as a molecular mechanism of ochratoxin A carcinogenicity. Chem Res Toxicol 25:252-262.
105. Pfohl-Leszkowicz A, Grosse Y, Kane A, Gharbi A, Baudrimont I, Obrecht S, Creppy EE, Dirheimer G. 1993. Is the oxydative pathway implicated in the genotoxicity of ochratoxin A? In: Human ochratoxicosis and related pathologies, Montrouge and London: Libbey J, eds, London Colloque INSERM, 231:177-187.
106. Pfohl-Leszkowicz A, Pinelli E, Bartsch H, Mohr U, Castegnaro M. 1998. Sex and Strain differences in ochratoxin A metabolism and DNA adduction in two strains of rats Mol Carcinogenesis 23:76-83.
107. Pfohl-Leszkowicz A, Bartsch H, Azémar B, Mohr U, Estève J, Castegnaro M. 2002. MESNA protects rats against nephrotoxicity but not carcinogenicity induced by ochratoxin A, implicating two separate pathways. Facta Universitatis Series Medicine and Biology 9:57-63.
108. Pfohl-Leszkowicz A, Tozlovanu M, Stepanovic J, Stefanovic V, Manderville R, Castegnaro M. 2006. Comparative genotoxicity of ochratoxin A and aristolochic acid in human kidney cells: interpretation of ongoing analyses of food, blood, urine and kidney tissue from Serbia. Colleg Antropologic Suppl 30:1-17.
109. Pfohl-Leszkowicz A, Tozlovanu M, Manderville R, Peraica M, Castegnaro M, Stefanovic V. 2007. New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in human nephropathy and urinary tract tumor. Mol Nutr Food Res 51:131-146.
110. Porter RS. 2004. The merck manual's online medical library. Whitehouse Station: Merck Research Lab.
111. Posea C, Sonea A, Birtoiu A, Roman M, Vasile M, Bensce A, Ion C. 2013. The presence of mycotoxins (OTA and ZEA) in feed for pigs and their influence on reproduction. Seria Med Vet 56:322-329.
112. Postupolski J, Karlowski K, Kubik P. 2006. Ochratoxin A in maternal and metal blood and in maternal milk. Rocz Panstw Zakl Hig 57:23-30.
113. Raymond CS, Murphy MW, O'Sullivan MG, Bardwell VJ, Zarkower D. 2000. Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev 14:2587-2595.
114. Rosner H, Rohrmann B, Peiker G. 2000. Ochratoxin A in human serum. Arch Lebensmittelhyg 51:104-107.
115. Schwartz GG, Manderville RA, Pfohl-Leszkowicz A. 2010. Response to comments of Peter G. Mantle. Toxins 2:2337-2339.
116. SCOOP. 2002. Assessment of dietary intake of Ochratoxin A by the population of EU member states. Reports on tasks for scientific cooperation TASK 3.2.7, European Commission, 153p.
117. Scott PM. 2005. Biomarkers of human exposure to ochratoxin A. Food Addit Contam 22(Suppl 1):99-107.
118. Shepard TH. 2001. Catalog of teratogenic agents. 10th ed. Baltimore, MD: Johns Hopkins University Press.
119. Shreeve BJ, Patterson DS, Pepin GA, Roberts BA, Wrathal AE. 1977. Effect of feeding ochratoxin A to pigs during early pregnancy. Br Vet J 133:412-417.
120. Simeone A, Gulisano M, Acampora D, Stornaiuolo A, Rambaldi M, Boncinelli E. 1992. Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex. EMBO J 11:2541-2550.
121. Skaug MA, Stormer FC, Saugstad OD. 1998. Ochratoxin A: a naturally occurring mycotoxin found in human milk samples from Norway. Acta Paediatr 87:1275-1278.
122. Solti L, Pécsi T, Barna-Vetró I, Szász F, Biró K, Szabo E. 1999. Analysis of serum and seminal plasma after feeding ochratoxin A with breeding boars. Anim Reprod Sci 56:123-132.
123. Speight TM, Holford NHG. 1997. Avery's drug treatment. 4th ed. Auckland: Adis International Limited. p 76-126.
124. Srinavasa J. 2011. Does ochratoxin A (OTA) cause testicular cancer in humans? Act Med Lituan 18:1-3.
125. Still PE, Macklin AW, Ribelin WE, Smalley EB. 1971. Relationship of ochratoxin A to fetal death in laboratory and domestic animals. Nature 234:563-564.
126. Storm EE, Rubenstein JL, Martin GR. 2003. Dosage of Fgf8 determines whether cell survival is positively or negatively regulated in the developing forebrain. Proc Natl Acad Sci USA 100:1757-1762.
127. Suda Y, Matsuo I, Kuratani S, Aizawa S. 1996. Otx1 function overlaps with Otx2 in development of mouse forebrain and midbrain. Genes Cells 1:1031-1044
128. Suda Y, Hossain ZM, Kobayashi C, Hatano O, Yoshida M, Matsuo I, Aizawa S. 2001. Emx2 directs the development of diencefalon in cooperation with Otx2. Development 128:2433-2450.
129. Thomas JL, Mayers RP, Strickler RC. 1989. Human placental 3[beta]-hydroxy-5-enesteroid dehydrogenase and steroid 5-4-ene-isomerase: purification from mitochondria and kinetic profiles, biophysical characterization of the purified mitochondrial and microsomal enzymes. J Steroid Biochem 33:209-217.
130. Tozlovanu M, Faucet-Marquis V, Pfohl-Leszkowicz A, Manderville Richard A. 2006. Genotoxicity of the hydroquinone metabolite of ochratoxin A: structure-activity relationships for covalent DNA adduction. Chem Res Toxicol 19:1241-1247.
131. Tozlovanu M, Canadas D, Pfohl Leszkowicz A, Frenette Ch, Paugh RJ, Manderville RA. 2012. Glutathione conjugates of ochratoxin A as biomarkers of exposure. Arh Hig Rada Toksikol 63:417-427.
132. Turnbull C, Rapley EA, Seal S, Pernet D, Renwick A, Hughes D, Ricketts M, Linger M, Nsengimana J, Delouhas P, Huddart RA, Bishop DT, Easton DF, Stratton MR, Rahman N. 2010. Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat Genet 42:604-608.
133. Ueta E, Kodama M, Sumino Y, Kurome M, Ohta Ki, Kataigiri Ri, Naruse I. 2010. Gender-dependent differences in the incidence of ochratoxin A-induced neural tube defects in the Pdn/Pdn mouse. Congenit Anom 50:29-39.
134. van Dorp DR, Malleis JM, Sullivan BP, Klein MD. 2010. Teratogens inducing congenital abdominal wall defects in animal models. Pediatr Surg Int 26:127-139.
135. Verma R, Chakraborty D. 2008. Emblica officinalis aqueous extract ameliorates ochratoxin induced lipid peroxidation in the testes of mice. Act Pol Pharm Drug Res 65(2):187-194.
136. Walum E, Flint OP. 1990. Midbrain micromass culture: a model for studies of teratogenic and subteratogenic effects on CNS development. Acta Physiol Scand 592(suppl 1):61-72.
137. Wang X, Wang M, Niu T, Chen Ch, Xu X. 1998. Microsomal epoxide hydrolase polymorphism and the risk of spontaneous abortion. Epidemiol 9:540-544.
138. 1. II. Histopatological features of teratogenical anomalies induced in fetuses. Birth Defects Res B Dev Reprod Toxicol 71:352-358
139. 1. I. Maternal toxicity and fetal malformations. Birt Def Res B Dev Reprod Toxicol 71:343-353.
140. Wangikar PB, Dwivedi P, Sinha N. 2004c. Teratogenic effects of ochratoxin A in rabbits. World Rabbit Sci 12:159-171.
141. 1 with special reference to microscopic effects. Toxicology 215:37-47.
142. 1 alone and in combination on post-implantation rat embryos in culture. J Turkish-German Gynecol Assoc 8:357-364.
143. Wei X, Sulik KK. 1993. Pathogenesis of craniofacial and body wall malformations induced by ochratoxin A in mice. Am J Med Gen 47:862-871.
144. Wei X, Sulik KK. 1996. Pathogenesis of caudal dysgenesis/sirenomelia induced by ochratoxin A in chick embryos. Teratology 53:378-391.
145. Wiger R., Stormer FC. 1990. Effects of ochratoxins A and B on prechondrogenic mesenchymal cells from chick embryo limb buds. Toxicol Lett 54:129-134.
146. Wijesinha S, Piterman L, Kirby CN. 2013. The male reproductive system - an overview of common problems. Aust Fam Physician 42:276-278.
147. Wilk-Zasadna I, Minta M. 2009. Developmental toxicity of ochratoxin A in rat embryo midbrain micromass cultures. Int J Mol Sci 10:37-49.
148. Woo CSJ, Partanen H, Myllynen P, Vähäkangas K, El Nezami-H. 2012. Fate of the teratogenic and carcinogenic ochratoxin A in human perfused placenta. Toxicol Lett 208:92-99.
149. Woo CSJ, Wang LMY, Ahokas J, El Nezami H. 2013. Potential endocrine disrupting effect of ochratoxin A on human placental 3 β hydroxysteroid dehydrogense/isomeras in JEG-3 cells at levels relevant to human exposure. Reprod Toxicol 38:47-52.
150. Wu Q, Dohnal V, Huang L, Kuca K, Wang X, Chen G, Yuan Z. 2011. Metabolic pathways of ochratoxin A. Curr Drug Metab 12:1-10.
151. Xiao H, Marquardt RR, Frohlich AA, Ling YZ. 1995. Synthesis and structural elucidation of analogs of ochratoxin A. J Agric Food Chem 43:524-530.
152. Xiao H, Madhyastha S, Marquardt R, Li S, Vodela J, Frohlich A, Kemppainen B. 1996. Toxicity of ochratoxin A, its opened lactone form and several of its analogs: Structure-activity relationships. Toxicol Appl Pharmacol 137:182-192.
153. Yoshida M, Suda Y, Matsuo I, Miyamoto N, Takeda N, Kuratani S, Aizawa S. 1997. Emx1 and Emx2 functions in development of dorsal telencefalon. Development 124:101-111.
154. Young LY, Koda-Kimble MA. 1995. Applied theraputics: the clinical use of drugs. 6th ed. Vancouver, WA: Applied Therapeutics. p 12-14.
155. Zimmerli B, Dick R. 1995. Determination of ochratoxin A at the ppt level in human blood, serum, milk and some foodstuffs by highperformance liquid chromatography with enhanced fluorescence detection and immunoaffinity column cleanup: methodology and Swiss data. J Chromatogr B Biomed Appl 666:85-99.
156. Zinedine A, Soriano JM, Molto JC, Manes J. 2007. Review on the toxicity, occurence, metabolism, detoxification, regulation and intake of zearalenone:an oestrogenic mycotoxin. Food Chem Toxicol 45:1-18.
157. Zusterzeel PLM, Nelen WLDM, Roelofs HMJ, Petrs WHM, Blom HJ, Steegers EAP. 2000. Polymorphisms in biotransformation enzymes and the risk for recurrent early pregnancy loss. Mol Hum Reprod 6:474-478.