Pubertal exposure to low doses of zearalenone disrupting spermatogenesis through ERα related genetic and epigenetic pathways

Gao, Yishan; Zhao, Yong; Zhang, Hongfu; Zhang, Pengfei; Liu, Jing; Feng, Yanni; Men, Yuhao; Li, Lan; Shen, Wei; Sun, Zhongyi; Liu, Min

doi:10.1016/j.toxlet.2019.08.007

Cited by 25 publications

(12 citation statements)

References 30 publications

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“…Exposure to zearalenone, a mycotoxin produced by Fusarium that acts via the ER signaling pathway to impair mouse spermatogenesis by producing elevated DNA double stranded breaks and decreasing the number of spermatogenic cells [ 191 ], has also been shown to promote a global decrease in DNA methylation, an increase in the methylation of histone marker H3K27 and a decrease of estrogen alpha in the testis of pubertal CD1 mice exposed to a dose lower than the no observed effect level (NOAEL). Concomitantly with these findings, the authors report the disruption of meiosis and decreased sperm quality [ 192 ]. Moreover, the same group—using the same doses—further explored the consequences of prenatal exposure to zearalenone in ICR mice and found that, irrespective of the strain used, a global reduction in both DNA methylation and estrogen alpha can still be observed, paralleled by elevated histone methylation of H3K9 and H3K27 [ 193 ].…”

Section: Epigenetic Mechanisms Are Sensitive To Environment and LImentioning

confidence: 76%

Environmental Impact on Male (In)Fertility via Epigenetic Route

Cescon

Chianese

Tavares

2020

JCM

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In the last 40 years, male reproductive health—which is very sensitive to both environmental exposure and metabolic status—has deteriorated and the poor sperm quality observed has been suggested to affect offspring development and its health in adult life. In this scenario, evidence now suggests that epigenetics shapes endocrine functions, linking genetics and environment. During fertilization, spermatozoa share with the oocyte their epigenome, along with their haploid genome, in order to orchestrate embryo development. The epigenetic signature of spermatozoa is the result of a dynamic modulation of the epigenetic marks occurring, firstly, in the testis—during germ cell progression—then, along the epididymis, where spermatozoa still receive molecules, conveyed by epididymosomes. Paternal lifestyle, including nutrition and exposure to hazardous substances, alters the phenotype of the next generations, through the remodeling of a sperm epigenetic blueprint that dynamically reacts to a wide range of environmental and lifestyle stressors. With that in mind, this review will summarize and discuss insights into germline epigenetic plasticity caused by environmental stimuli and diet and how spermatozoa may be carriers of induced epimutations across generations through a mechanism known as paternal transgenerational epigenetic inheritance.

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Section: Epigenetic Mechanisms Are Sensitive To Environment and LImentioning

confidence: 76%

Environmental Impact on Male (In)Fertility via Epigenetic Route

Cescon

Chianese

Tavares

2020

JCM

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“…Previous studies have reported that zearalenone (ZEA) is one of the mycotoxins that exist in contaminated food [ 29 ]. Zearalenone has been found to impair male reproduction, reducing semen quality and impeding spermatogenesis [ 7 , 30 ]. The results of this study showed that after 5 weeks of ZEA (30 μg/kg) treatment, the ZEA treatment group significantly reduced the sperm motility, concentration, and sperm motility parameters of mice.…”

Section: Discussionmentioning

confidence: 99%

“…It affects meat and dairy products consumed by humans thus posing a serious threat to animal and human health [ 4 , 5 ]. Previous studies showed that ZEA not only causes cytotoxicity [ 6 ], genetic toxicity [ 7 ], and immunotoxicity [ 8 ] in domestic animals but also affects the normal operation of the estrogen signaling pathway leading to animal reproductive toxicity [ 9 ]. Previous studies have shown that ZEA exposure can reduce the semen quality of male mice, increase the rate of spermatogenic cell apoptosis, hinder spermatogenesis, and thus impair male reproductive function [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Zearalenone-Induced Ferroptosis on Mice Spermatogenesis

Zhu

Cui

Ding

et al. 2022

Animals

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Male reproductive health is critically worsening around the world. It has been reported that the mycotoxin ZEA causes reproductive toxicity to domestic animals and affects spermatogenesis, thereby inhibiting male reproductive function. Ferroptosis is a newly identified type of programmed cell death that is different from apoptosis and it depends on iron accumulation and lipid peroxidation. Whether ferroptosis is linked to ZEA’s detrimental effect on spermatogenesis needs to be further explored. This study clarifies ferroptosis’s involvement in ZEA-induced damage on spermatogenesis. The reproductive injury model used in this study was induced by gavaging male mice in the ZEA treatment group with 30 μg/kg of ZEA for five weeks. Results show that ZEA treatment reduced mouse sperm motility and concentration, destroyed the structure of the seminiferous tubules of the testis, damaged the antioxidant defense system, and blocked spermatogenesis. Ferrostatin-1 (Fer-1) inhibition of ferroptosis partially alleviated ZEA-induced oligozoospermia in mice. In addition, ZEA treatment was found to activate a signaling pathway associated with ferroptosis in mouse testis. ZEA also downregulated the expression of Nrf2, SLC7A11, and GPX4, and decreased the protein expression of SLC7A11 and GPX4, resulting in the accumulation of lipid peroxides and an increase in the level of 4-HNE protein in the testis. Importantly, these changes were accompanied by an increase in the relative contents of Fe2+ and Fe3+. Iron accumulation and lipid peroxidation are the causes of ferroptosis in spermatogenic cells, leading to a decrease in sperm motility and concentration. While the administration of Fer-1 at 0.5 and 1 mg/kg also increased the expression of SLC7A11 and GPX4 proteins by upregulating Nrf2 expression, reducing iron accumulation, and reversing ZEA-induced ferroptosis, Fer-1 at 1.5 mg/kg had the best repairing effect for all parameters. In conclusion, ZEA-induced ferroptosis may be mediated by a notable reduction in Nrf2, SLC7A11 and GPX4 expression levels. Overall, ferroptosis is a novel therapeutic target for mitigating ZEA-induced reproductive toxicity.

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“…Similar to estradiol, ZEA has been shown to exert negative effects on sperm cell, Sertoli cells, and Leydig cells. These include altered concentration, viability, motility, DNA integrity and apoptotic rate of sperm cells; such altered biological functions and apoptotic rates of Sertoli and Leydig cells have been reported in several model systems [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. These processes are also manifested in altered structure of seminiferous tubules and weight of the testis [ 49 , 50 ].…”

Section: Overview Of the Pathogenesis Of Zearalenonementioning

confidence: 99%

Estrogenic and Non-Estrogenic Disruptor Effect of Zearalenone on Male Reproduction: A Review

Balló

Székvári²,

Czétány

et al. 2023

IJMS

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According to some estimates, at least 70% of feedstuffs and finished feeds are contaminated with one or more mycotoxins and, due to its significant prevalence, both animals and humans are highly likely to be exposed to these toxins. In addition to health risks, they also cause economic issues. From a healthcare point of view, zearalenone (ZEA) and its derivatives have been shown to exert many negative effects. Specifically, ZEA has hepatotoxicity, immunotoxicity, genotoxicity, carcinogenicity, intestinal toxicity, reproductive toxicity and endocrine disruption effects. Of these effects, male reproductive deterioration and processes that lead to this have been reviewed in this study. Papers are reviewed that demonstrate estrogenic effects of ZEA due to its analogy to estradiol and how these effects may influence male reproductive cells such as spermatozoa, Sertoli cells and Leydig cells. Data that employ epigenetic effects of ZEA are also discussed. We discuss literature data demonstrating that reactive oxygen species formation in ZEA-exposed cells plays a crucial role in diminished spermatogenesis; reduced sperm motility, viability and mitochondrial membrane potential; altered intracellular antioxidant enzyme activities; and increased rates of apoptosis and DNA fragmentation; thereby resulting in reduced pregnancy.

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Pubertal exposure to low doses of zearalenone disrupting spermatogenesis through ERα related genetic and epigenetic pathways

Cited by 25 publications

References 30 publications

Environmental Impact on Male (In)Fertility via Epigenetic Route

Environmental Impact on Male (In)Fertility via Epigenetic Route

Effect of Zearalenone-Induced Ferroptosis on Mice Spermatogenesis

Estrogenic and Non-Estrogenic Disruptor Effect of Zearalenone on Male Reproduction: A Review

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