Effects of Fusarium mycotoxins on steroid production by porcine granulosa cells

Ranzenigo, G.; Caloni, F.; Crémonesi, F.; Aad, Pauline Y.; Spicer, L. J.

doi:10.1016/j.anireprosci.2007.06.023

Cited by 82 publications

(63 citation statements)

References 54 publications

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“…ERα activation/interactions has been evident at picomolar or nanomolar concentrations using tests covering different steps of the estrogenic response: binding affinity (Takemura et al, 2007), activation of transcriptional activation (Frizzell et al, 2011), proliferation of MCF7 cells (Molina-Molina et al, 2014;Shier et al, 2001) and yeast transfected with ERα (Bovee et al, 2004), as well as results on transcriptional activation (ERα CALUX ® ) and receptor-ligand translocation (ERα redistribution assay), as obtained in this study. Active concentrations (pico to nanomolar range: this study, and studies aforementioned) were found to be much lower than the levels required to alter steroid metabolism (micromolar range, for examples see: (Frizzell et al, 2011;Gracia et al, 2007;Kolle et al, 2012;Ranzenigo et al, 2008;Yang et al, 2007). Interestingly, estrogen may stimulate activities of enzymes of steroidogenesis such as aromatase via ER-mediated regulation (Lee et al, 2012).…”

Section: Tab 2: Computed Results Of Zen and Reduced Derivativesmentioning

confidence: 98%

“…It has been well established that ZEN and metabolites activate estrogen receptors α and β (Bovee et al, 2004;Bravin et al, 2009;EFSA, 2011;Frizzell et al, 2011;Shier et al, 2001;Takemura et al, 2007;WHO, 2000). It has also been suggested that these molecules may alter steroidogenesis (Frizzell et al, 2011;Gracia et al, 2007;Kolle et al, 2012;Ranzenigo et al, 2008;Yang et al, 2007) and may act as an antagonist of the androgenic receptor (Molina-Molina et al, 2014). Undoubtedly, ZEN and metabolites might perturbate several toxicological pathways, but based on the body of available data and reviews from regulatory agencies, the critical effects are thought to result from estrogenic activity mainly through an activation of ERα (EFSA, 2011;Kuiper et al, 1997;WHO, 2000).…”

Section: Tab 2: Computed Results Of Zen and Reduced Derivativesmentioning

confidence: 99%

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Hazard assessment through hybrid in vitro / in silico approach: The case of zearalenone

Ehrlich

2015

ALTEX

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SummaryWithin the framework of reduction, refinement and replacement of animal experiments, new approaches for identification and characterization of chemical hazards have been developed. Grouping and read-across has been promoted as a most promising alternative approach. It uses existing toxicological information on a group of chemicals to make predictions on the toxicity of uncharacterized ones. In the present work, the feasibility of applying in vitro and in silico techniques to group chemicals for read-across was studied using the food mycotoxin zearalenone (ZEN) and metabolites as a case study. ZEN and its reduced metabolites are known to act through activation of the estrogen receptor α (ERα). The ranking of their estrogenic potencies appeared highly conserved across test systems including binding, in vitro and in vivo assays. This data suggests that activation of ERα may play a role in the molecular initiating event (MIE) and be predictive of adverse effects, and it provides the rationale to model receptor-binding for hazard identification. The investigation of receptor-ligand interactions through docking simulation proved to accurately rank estrogenic potencies of ZEN and reduced metabolites, showing the suitability of the model to address estrogenic potency for this group of compounds. Therefore, the model was further applied to biologically uncharacterized, commercially unavailable, oxidized ZEN metabolites (6α-, 6β-, 8α-, 8β-, 13-and 15-OH-ZEN). Except for 15-OH-ZEN, the data indicate that in general, the oxidized metabolites would be considered of lower estrogenic concern than ZEN and reduced metabolites.

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Section: Tab 2: Computed Results Of Zen and Reduced Derivativesmentioning

confidence: 98%

Section: Tab 2: Computed Results Of Zen and Reduced Derivativesmentioning

confidence: 99%

Hazard assessment through hybrid in vitro / in silico approach: The case of zearalenone

Ehrlich

2015

ALTEX

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“…Endogenous oestrogens generally inhibit proliferation, stimulate differentiation, and promote apoptosis. According to Ranzenigo et al (2008), phytoestrogens elicit a similar response, whereas small doses of ZEN exert a chemo protective effect, but ZEN in higher doses inhibits the proliferation in specific tissues. Scientific data are scarce in terms of documenting the effect of very low ZEN doses (i.e., No Observed Adverse Effect Level -NOAEL values), and/or less than <40 μg/kg body weight (BW) (Boermans and Leung 2007).…”

Section: Introductionmentioning

confidence: 99%

The effect of experimental low zearalenone intoxication on ovarian follicles in pre-pubertal bitches

Gajęcka¹

2013

Polish Journal of Veterinary Sciences

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Companion animals, including bitches, may be exposed to zearalenone (ZEN) toxins that are often present in feed, and ZEN intoxication may lead to ovarian dysfunction. This study involved evaluation of the degree of ZEN-induced hypo stimulation of ovary by determination of proliferative and apoptotic indices and description of the ultra-structural organization of ovarian follicles in pre-pubertal bitches subjected to experimental, long-term exposure to low-dose ZEN mycotoxicosis. The experiment involved 30 clinically healthy, immature Beagle bitches aged approximately 70 days with initial average body weight of 8 kg, randomly divided into three groups of 10 animals each: two experimental groups (EI and EII) and a control group (C). Over a period of 42 days, ZEN was administered per os to EI animals at a dose of 50 μg/kg BW, and to EII bitches at a dose of 75 μg/kg BW. Control group animals were fed placebo containing no ZEN for 42 days. Analytical samples of the mycotoxin were administered daily in gelatin capsules before morning feeding. All the bitches were subjected to ovario-hysterectomy at the end of the experiment. Proliferation index (PCNA method) and apoptotic index (TUNEL test) values were determined by immune-histological analyses. The median for apoptotic index was determined at 13.45 for group EI, 17.84 for group EII, and 8.59 for group C. The median for proliferation index was determined at 35.25 for group EII, 42.44 for group EI, and 70.60 for group C. The results of ultra-structural examinations of the ovaries revealed that experimental, ZEN-induced hyperestrogenism enhanced apoptosis and lowered the proliferative ability of follicular cells what contributed to organelle destruction in pre-pubertal bitches. The changes observed were particularly advanced in EII animals, which were administered a higher dose of ZEN.

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“…Recent research indicated that feeding feed to gilts contaminated with low concentrations of zearalenone (0.235 to 0.358 ppm) significantly reduced the intrinsic quality of the oocyte collected from these animals (Alm et al, 2006). The level of contamination has dose dependent effects on granulosa cells, steroidogenesis and gene expression Ranzenigo et al, 2008).…”

Section: Giltsmentioning

confidence: 99%

“…The feeding of contaminated feed containing DON (Table 4), as well as decreasing food intake, can influence the immune system (cellular and humoral), effect metabolic disturbances in liver and spleen mainly due to inhibition of RNA, DNA and protein synthesis (Smith and Az-Llano, 2009), and cause reproductive alterations resulting in decreased oocyte and embryo development (Tiemann and Danicke, 2007;Ranzenigo et al, 2008). Prepuberal gilts react more sensitively to DON > ZEA feeding compared to pregnant sows.…”

Section: Desoxynivalenol (Don)mentioning

confidence: 99%

The role of mycotoxins in pig reproduction: a review

Kanora¹,

Maes²

2009

Vet. Med.

101

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ABSTRACT:Mycotoxins are commonly present in feed for farm animals. Sows and gilts are highly susceptible to mycotoxins. This article presents a review describing the main mycotoxins encountered in pig feed which have a negative impact on sow fertility and reproduction. Consumption of feed that is contaminated with these mycotoxins may cause a variety of symptoms, depending on the type of mycotoxin, quantity and duration of exposure, as well as the health status and condition of the animal at the time of exposure. Two types of fungi are recognized, field fungi and storage fungi. Field fungi such as Fusarium spp., Aspergillus spp. and Claviceps spp. may produce toxins that lead to disturbed reproductive performance. Storage fungi occur if the humidity during storage is too high. In daily practice, the symptoms related to mycotoxicosis can occur at toxin concentrations below the detection limit. Knowledge of the effects of mycotoxins is expanding rapidly. Mycotoxins may still be present in feedstuffs despite negative analytical findings and because of the presence of hot spots in feed and or feedstuffs. Clinical symptoms can be very pronounced, making the diagnosis for the practitioner quite easy but in many cases the symptoms are vague and not at all present at herd level on a regular basis. The practitioner is in the first line of raising awareness in all parties whenever the first indication exists of a possible mycotoxicosis problem causing reproductive failure in breeding pigs. The problems can be resolved only if all parties involved in pig herd health take the necessary preventive measures and actions. The main toxins causing reproductive failure discussed in this article are aflatoxins, ergot alkaloids, trichothecenes and zearalenone.

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Effects of Fusarium mycotoxins on steroid production by porcine granulosa cells

Cited by 82 publications

References 54 publications

Hazard assessment through hybrid in vitro / in silico approach: The case of zearalenone

Hazard assessment through hybrid in vitro / in silico approach: The case of zearalenone

The effect of experimental low zearalenone intoxication on ovarian follicles in pre-pubertal bitches

The role of mycotoxins in pig reproduction: a review

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