Multigenerational exposure to dietary zearalenone (ZEA), an estrogenic mycotoxin, affects puberty and reproduction in female mice

Zhao, Fei; Li, Rong; Xiao, Shuo; Diao, Honglu; Zowalaty, Ahmed E. El; Ye, Xiaoqin

doi:10.1016/j.reprotox.2014.06.005

Cited by 29 publications

(16 citation statements)

References 23 publications

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“…Zearalenone (ZEA) is a toxic compound produced by several species of Fusarium and is found to cause mycotoxicosis in animals and humans [ 1 ]. It usually exists in contaminated livestock feed consumed by domestic animals, and is subsequently hazardous to the metabolism of organisms remarkably [ 2 , 3 ]. It is well known that both in females and males, the regulation of estrogen signaling is important in maintaining the normal functionality of reproductive systems [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress Induced by Zearalenone in Porcine Granulosa Cells and Its Rescue by Curcumin In Vitro

et al. 2015

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Oxidative stress (OS), as a signal of aberrant intracellular mechanisms, plays key roles in maintaining homeostasis for organisms. The occurrence of OS due to the disorder of normal cellular redox balance indicates the overproduction of reactive oxygen species (ROS) and/or deficiency of antioxidants. Once the balance is broken down, repression of oxidative stress is one of the most effective ways to alleviate it. Ongoing studies provide remarkable evidence that oxidative stress is involved in reproductive toxicity induced by various stimuli, such as environmental toxicants and food toxicity. Zearalenone (ZEA), as a toxic compound existing in contaminated food products, is found to induce mycotoxicosis that has a significant impact on the reproduction of domestic animals, especially pigs. However, there is no information about how ROS and oxidative stress is involved in the influence of ZEA on porcine granulosa cells, or whether the stress can be rescued by curcumin. In this study, ZEA-induced effect on porcine granulosa cells was investigated at low concentrations (15 μM, 30 μM and 60 μM). In vitro ROS levels, the mRNA level and activity of superoxide dismutase, glutathione peroxidase and catalase were obtained. The results showed that in comparison with negative control, ZEA increased oxidative stress with higher ROS levels, reduced the expression and activity of antioxidative enzymes, increased the intensity of fluorogenic probes 2’, 7’-Dichlorodihydrofluorescin diacetate and dihydroethidium in flow cytometry assay and fluorescence microscopy. Meanwhile, the activity of glutathione (GSH) did not change obviously following 60 μM ZEA treatment. Furthermore, the underlying protective mechanisms of curcumin on the ZEA-treated porcine granulosa cells were investigated. The data revealed that curcumin pre-treatment significantly suppressed ZEA-induced oxidative stress. Collectively, porcine granulosa cells were sensitive to ZEA, which may induce oxidative stress. The findings from this study clearly demonstrate that curcumin is effective to reduce the dysregulation of cellular redox balance on porcine granulosa cells in vitro and should be further investigated for its protective role against ZEA in animals.

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Section: Introductionmentioning

confidence: 99%

Oxidative Stress Induced by Zearalenone in Porcine Granulosa Cells and Its Rescue by Curcumin In Vitro

et al. 2015

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“…Vaginal opening has been used as an early indicator of pubertal onset in rodents. It can be regulated by estrogen signaling because estrogenic endocrine disruptors could promote vaginal opening 19 20 21 22 23 , while anti-estrogens could delay vaginal opening 29 30 and estrogen signaling deficiency could lead to vaginal imperforation 31 in rodents. Vaginal imperforation has been observed in several mouse models, such as β-catenin C429S 32 , double deficiency of Bak and Bax 33 , over-expression of Bcl2 34 , triple deficiency of Bid, Bim, and Puma 35 , triple deficiency of Tyro3, Axl, and Mer 36 , deficiency of p63 37 , Movo1 38 , Pax8 39 , Grb10 40 , Glypican-3 41 , Map3k1 42 , EphA1 43 , Vangl2 44 , or Lrp2/Megalin 31 .…”

Section: Discussionmentioning

confidence: 99%

“…During the study of endocrine disruptors, we found that a few estrogenic endocrine disruptors could promote vaginal opening 19 20 21 22 23 , an early indicator of pubertal onset in mice 24 25 26 27 28 . It was our initial intention to use this Lhfpl2 mutant as a loss-of-function model for studying mechanisms of vaginal opening, which are not well understood.…”

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confidence: 99%

Novel function of LHFPL2 in female and male distal reproductive tract development

Zhao

Zha

et al. 2016

Sci Rep

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Congenital reproductive tract anomalies could impair fertility. Female and male reproductive tracts are developed from Müllerian ducts and Wolffian ducts, respectively, involving initiation, elongation and differentiation. Genetic basis solely for distal reproductive tract development is largely unknown. Lhfpl2 (lipoma HMGIC fusion partner-like 2) encodes a tetra-transmembrane protein with unknown functions. It is expressed in follicle cells of ovary and epithelial cells of reproductive tracts. A spontaneous point mutation of Lhfpl2 (LHFPL2G102E) leads to infertility in 100% female mice, which have normal ovarian development, ovulation, uterine development, and uterine response to exogenous estrogen stimulation, but abnormal upper longitudinal vaginal septum and lower vaginal agenesis. Infertility is also observed in ~70% mutant males, which have normal mating behavior and sperm counts, but abnormal distal vas deferens convolution resulting in complete and incomplete blockage of reproductive tract in infertile and fertile males, respectively. On embryonic day 15.5, mutant Müllerian ducts and Wolffian ducts have elongated but their duct tips are enlarged and fail to merge with the urogenital sinus. These findings provide a novel function of LHFPL2 and a novel genetic basis for distal reproductive tract development; they also emphasize the importance of an additional merging phase for proper reproductive tract development.

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“…ZEA doses of 0 ppm (control), 0.8 ppm, 4 ppm, 10 ppm, and 40 ppm in the diets were used in our previous postweaning, premating, postmating, and/or multigenerational studies in mice [31,34]. These ZEA levels have been reported in the contaminated food [1][2][3][4], which must also have contamination of other mycotoxins, including other mycoestrogens.…”

Section: Dose Selection Treatment and Tissue Collectionmentioning

confidence: 99%

Dietary exposure to mycotoxin zearalenone (ZEA) during post-implantation adversely affects placental development in mice

Andersen

et al. 2019

Reproductive Toxicology

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Zearalenone (ZEA) is a common food contaminant (ppb~ppm) derived from Fusarium fungi. With its estrogenicity and potential chronic exposure, ZEA poses a risk to pregnancy. Our previous studies implied post-implantational lethality by ZEA. Since a functional placenta is essential for fetal development and survival, it was hypothesized that ZEA may have adverse effects on placental development leading to post-implantational lethality. Exposure of young mice to 0, 0.8, 4, 10, and 40 ppm ZEA diets from gestation day 5.5 (D5.5) to D13.5 led to increased resorption of implantation sites, increased placental hemorrhage, decreased placental and fetal weights, proportionally reduced placental layers, and disorganized placental labyrinth vascular spaces in the 40 ppm ZEA group, as well as lipid accumulation in the labyrinth layer of all four ZEA treatment groups examined on D13.5. These data demonstrate adverse effects of ZEA on placental development.

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Multigenerational exposure to dietary zearalenone (ZEA), an estrogenic mycotoxin, affects puberty and reproduction in female mice

Cited by 29 publications

References 23 publications

Oxidative Stress Induced by Zearalenone in Porcine Granulosa Cells and Its Rescue by Curcumin In Vitro

Oxidative Stress Induced by Zearalenone in Porcine Granulosa Cells and Its Rescue by Curcumin In Vitro

Novel function of LHFPL2 in female and male distal reproductive tract development

Dietary exposure to mycotoxin zearalenone (ZEA) during post-implantation adversely affects placental development in mice

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