title: Influence of mycotoxin zearalenone and its derivatives (alpha and beta zearalenol) on apoptosis and proliferation of cultured granulosa cells from equine ovaries.
abstract: BACKGROUND
  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.
authors.affiliation: Institute of Sciences of Food Production (ISPA), National Research Council (CNR), Via Amendola 122/O, 70124 Bari, Italy. fiorenza.minervini@ispa.cnr.it
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Minervini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giannoccaro
authors.forename: Francesca
authors.initials: F
authors.lastname: Fornelli
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Dell'Aquila
authors.forename: Paolo
authors.initials: P
authors.lastname: Minoia
authors.forename: Angelo
authors.initials: A
authors.lastname: Visconti
mesh_terms: D000821:Animal Feed; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005496:Follicular Atresia / Q000187:drug effects; D005506:Food Contamination; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects*; D006736:Horses; D015025:Zearalenone / Q000494:pharmacology*; D015029:Zeranol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004968:Estrogens, Non-Steroidal; C029659:zearalenol; D015025:Zearalenone; D015029:Zeranol; D004247:DNA