In vitro effects of deoxynivalenol and zearalenone major metabolites alone and combined, on cell proliferation, steroid production and gene expression in bovine small-follicle granulosa cells

Pizzo, Fabiola; Caloni, F.; Schreiber, Nicole B.; Cortinovis, C.; Spicer, L. J.

doi:10.1016/j.toxicon.2015.11.018

Cited by 47 publications

(45 citation statements)

References 67 publications

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“…DON gets absorbed into the systemic circulation in calves and cows suffering from subacute rumen acidosis with digestive systems that are not fully functional (Abdela, ; Daenicke, Keese, Goyarts, & Döll, ). In vitro studies on the reproductive effects of DON in cattle have shown that it impairs in vitro cell proliferation, steroid production and granulosa cell (GC) gene expression (Pizzo, Caloni, Schreiber, Cortinovis, & Spicer, ).…”

Section: Introductionmentioning

confidence: 99%

Deoxynivalenol induces oxidative stress, inflammatory response and apoptosis in bovine mammary epithelial cells

Wang

Jin

et al. 2019

Animal Physiology Nutrition

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Deoxynivalenol (DON) is a toxic secondary metabolite produced by Fusarium graminearum. It is one of the most common feed contaminants that poses a serious threat to the health and performance of dairy cows. This study investigated the in vitro cytotoxicity of DON on bovine mammary epithelial cells (MAC‐T). DON at different concentrations (0.25, 0.3, 0.5, 0.8, 1 or 2 μg/ml) inhibited the growth of MAC‐T cells after 24 hr of exposure (p < .001). DON at 0.25 μg/ml increased lactate dehydrogenase (LDH) leakage (p < .05); decreased glutathione (GSH) levels (p < .001), total superoxide dismutase (T‐SOD) activity and total antioxidant capacity (T‐AOC; p < .01); and increased malondialdehyde (MDA) concentration (p < .01) in MAC‐T cells after 24 hr of exposure. We also observed that DON increased reactive oxygen species (ROS) levels in cells incubated for 9, 15 and 24 hr (p < .001). DON at 0.25 μg/ml triggered oxidative damage in MAC‐T cells. Furthermore, it induced an inflammatory response in the cells incubated for 9, 15 and 24 hr (p < .05) by increasing the mRNA expression levels of nuclear factor kappa B, myeloid differentiation factor 88 (MyD88), tumour necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), IL‐6, cyclooxygenase‐2 and IL‐8. We further examined the effect of DON on apoptosis. DON prevented normal proliferation of MAC‐T cells by blocked cell cycle progression in 24 hr (p < .001). In addition, the apoptosis rate measured using annexin V‐FITC significantly increased (p < .05) with increase in the mRNA expression level of Bax (p < .01) and increase in the Bax/Bcl‐2 ratio (p < .01) in cells incubated for 24 hr. In summary, DON exerts toxic effects in MAC‐T cells by causing oxidative stress, inducing an inflammatory response, affecting cell cycle and leading to apoptosis.

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Section: Introductionmentioning

confidence: 99%

Deoxynivalenol induces oxidative stress, inflammatory response and apoptosis in bovine mammary epithelial cells

Wang

Jin

et al. 2019

Animal Physiology Nutrition

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“…DON is also known to induce oxidative stress in cells (Savard et al, ); thus, it might be postulated that DON also regulates miR‐98 regulating CYP19A1 expression in hypoxic cells (Yu et al, ). It is also possible that observed changes in expression of steroidogenic genes after exposure of DON (Pizzo et al, ) are also regulated by miRNAs, though this hypothesis needs to be confirmed by further research studies both in vitro as well as in vivo.…”

Section: Deoxynivalenol and Steroidogenesismentioning

confidence: 99%

“…The effects of impaired steroidogenesis are not only disturbances in fertility, but also changes in steroid hormone concentrations: testosterone, progesterone and estradiol. DON is reported to modulate the secretion of progesterone from granulosa cells; both increases and decreases in its levels, dependent on the concentration of DON (Pizzo, Caloni, Schreiber, Cortinovis, & Spicer, ; Pizzo, Caloni, Schutz, Totty, & Spicer, ; Savard, Nogues, Boyer, & Chorfi, ). Decreased testosterone concentration was observed after DON administration in rats (Sprando et al, ) as well as decreased concentration of estradiol and cortisol in the human H295R cell line (Ndossi et al, ).…”

Section: Deoxynivalenol and Steroidogenesismentioning

confidence: 99%

“…Decreased testosterone concentration was observed after DON administration in rats (Sprando et al, ) as well as decreased concentration of estradiol and cortisol in the human H295R cell line (Ndossi et al, ). Estradiol production was also inhibited by DON (Guerrero‐Netro et al, ; Pizzo et al, , ). The doses of DON and observed effects are summarized in Table .…”

Section: Deoxynivalenol and Steroidogenesismentioning

confidence: 99%

“…Moreover, the process of steroidogenesis involves synthesis of several enzymes to catalase the production of steroids, which can be disturbed by DON through interference with the 60S ribosomal subunit and termination of translation (Zhou et al, ). On the other hand, DON might directly disturb the expression of steroidogenic enzymes, CYP11A1 and CYP19A1 (Pizzo et al, ) as well as modulate the expression of StAR protein in activated Leydig cells (Savard et al, ). A reduction in the StAR protein might be also associated with Nr4a1 downregulation as well as Lhr, which are both regulatory proteins of StAR (Savard et al, ).…”

Section: Deoxynivalenol and Steroidogenesismentioning

confidence: 99%

See 2 more Smart Citations

Deoxynivalenol as potential modulator of human steroidogenesis

Urbanek

Habrowska-Górczyńska

Kowalska

et al. 2018

J of Applied Toxicology

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Deoxynivalenol (DON) is a type B trichothecene, produced by the Fusarium species. Exposure to DON might cause disruptive effects such as reduced weight gain, neuroendocrine changes and immune modulation in animals (rats, dogs, pigs). There is huge concern that similar effects can be observed in humans. DON is a potential regulator of intracellular steroidogenesis. It is also possible that DON will be involved in the regulation of miRNAs connected with steroidogenesis. This review summarizes the latest knowledge about the influence of DON on steroidogenesis and human hormonal balance.

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Effects of the mycotoxin metabolite de‐epoxy‐deoxynivalenol (DOM‐1) on embryo development and sperm motility in cattle

Guerrero-Netro

Barreta

Costa

et al. 2020

J of Applied Toxicology

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Contamination of animal feed with Fusarium spp results in accumulation of mycotoxins including deoxynivalenol. In animals, deoxynivalenol is metabolized to de‐epoxy deoxynivalenol (DOM‐1), which is generally considered to be a non‐toxic metabolite; however, recent studies demonstrated that DOM‐1 can reduce steroid production and induce apoptosis in the bovine ovary. The objectives of this study were to assess the effects of DOM‐1 on applied aspects of reproductive function in cattle, specifically sperm function and embryo development in vitro and follicle growth and superovulatory responses in vivo. The effect of naturally contaminated feed on superovulatory responses was assessed; a dose of 6 ppm deoxynivalenol increased blood DOM‐1 concentrations to 20 ng/ml, but this did not alter the number of viable embryos recovered on day 7. However, intrafollicular injection of DOM‐1 (100 ng/ml) directly into the growing dominant follicle resulted in cessation of follicular growth over the subsequent 3 days. Treatment with DOM‐1 reduced motility of bull spermatozoa over a 10‐h period in vitro. Addition of DOM‐1 to oocytes in vitro during IVM did not alter rates of cumulus expansion and nuclear maturation, but treatment during IVF reduced the rate of blastocyst formation. These data illustrate that DOM‐1 is more biologically active than previously thought and negatively impacted reproductive outcomes in cattle.

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In vitro effects of deoxynivalenol and zearalenone major metabolites alone and combined, on cell proliferation, steroid production and gene expression in bovine small-follicle granulosa cells

Cited by 47 publications

References 67 publications

Deoxynivalenol induces oxidative stress, inflammatory response and apoptosis in bovine mammary epithelial cells

Deoxynivalenol induces oxidative stress, inflammatory response and apoptosis in bovine mammary epithelial cells

Deoxynivalenol as potential modulator of human steroidogenesis

Effects of the mycotoxin metabolite de‐epoxy‐deoxynivalenol (DOM‐1) on embryo development and sperm motility in cattle

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