Exploration of ZEA cytotoxicity to mouse endometrial stromal cells and RNA-seq analysis

Xie, Haiqiang; Hu, Jin; Cheng, Xiangdong; Dai, Yujian; Xiao-lin, Ding; Xu, Yinxue

doi:10.1002/jbt.21874

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…Our results demonstrated that ZEA dramatically decreased the growth of porcine granulosa cells in a dose and time dependent manner, and caused a significant increase in apoptotic cells. It was of note that in a previous report from other groups, ZEA exposure led to apoptosis in porcine splenic lymphocytes, immortalized goat Leydig cells, and endometrial stromal cells 32 , 47 , 48 . Next, ZEA exposure considerably altered the mRNA expression of genes in the granulosa cells using an RNA-seq approach, and the DEGs were found to be involved in cellular processes, molecular functions, and biological processes that were closely associated with cell proliferation, cell cycle, apoptosis, and DNA damage repair.…”

Section: Discussionmentioning

confidence: 79%

“…The ATM pathway is responsible primarily for DNA-DSBs, ZEA exposure induced oxidative DNA-DSBs and the expression of ATM, and an increase in the concentration of ZEA further increased DNA damage 24 , 31 . It has been found that ZEA can arrest the cell cycle at S and G2/M phases to block DNA replication in some somatic cells of the reproductive system 32 . However, it is unknown the influence of ZEA on genomic stability of ovarian granulosa cells which played vital roles during oocytes growth and development.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mycotoxin zearalenone exposure impairs genomic stability of swine follicular granulosa cells in vitro

Liu¹,

Wu²,

Sun³

et al. 2018

Int. J. Biol. Sci.

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Zearalenone (ZEA), a metabolite of Fusarium fungi, is commonly found on moldy grains. Because it can competitively combine to estrogen receptor to disrupt estrogenic signaling, it has been reported to have serious adverse effects on animal reproduction systems. In order to explore the genotoxic effects of ZEA exposure on ovarian somatic cells, porcine granulosa cells were exposed to 10 μM and 30 μM ZEA for 24 or 72 h in vitro. The results showed that ZEA exposure for 24 h remarkably reduced the proliferation of porcine granulosa cells in a dose-dependent manner as determined by MTT analysis and flow cytometry. Furthermore, exposure to ZEA for 72 h induced apoptosis, and RNA sequence analysis also revealed that the expression of apoptosis related genes were altered. RT-qPCR, immunofluorescence and western blot analysis further confirmed the expression of DNA damage and repair related genes (γ-H2AX, BRCA1, RAD51 and PRKDC) were increased in ZEA exposed granulosa cells. When the estrogen antagonist, tamoxifen, was added with ZEA in the culture medium, the DNA damage and repairment by ZEA returned to normal level. Collectively, these results illustrate that ZEA disrupts genome stability and inhibits growth of porcine granulosa cells via the estrogen receptors which may promote granulosa cell apoptosis when the DNA repair system is not enough to rescue this serious damage.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Mycotoxin zearalenone exposure impairs genomic stability of swine follicular granulosa cells in vitro

Liu¹,

Wu²,

Sun³

et al. 2018

Int. J. Biol. Sci.

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“…While BCL-2 guards against apoptosis, BAX is a promoter of apoptosis and a higher BAX/BCL-2 ratio favors a greater rate of apoptosis. Xie, Hu [ 118 ] also reported decreased cell viability in mouse endometrial stromal cells after ZEN exposure (>50 µM). Other cytotoxicity markers were enhanced including cell shrinkage, disruption of the cell cycle, and differential expression of genes related to cell cycle and apoptosis such as Bec-2 family , Cdc genes and Hoaxa-10 .…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, recent studies in porcine endometrial cells indicate that ZEN can activate the WNT/β-catenin signaling pathway to promote proliferation [ 123 ]. Overall, the evidence from murine models points toward strong apoptotic effects of mycoestrogens in the uterus and decreased cell viability in endometrial stromal and granulosa porcine-derived cells [ 101 , 118 , 120 ].…”

Section: Resultsmentioning

confidence: 99%

Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review

Kinkade

Rivera‐Núñez

Gorcyzca

et al. 2021

Toxins

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Contamination of the world’s food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN’s synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000–2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies (n = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified.

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“…Cells were exposed to 75, 100, 125 μM ZEA for 24 hours according to the previous experimental results, and they correspond to experimental group 1 (EG1), experimental group 2 (EG2), and experimental group 3 (EG3), respectively. In the experiments, dimethyl sulphoxide (DMSO) as the solvent reagent of ZEA.…”

Section: Methodsmentioning

confidence: 99%

ZEA exerts toxic effects on reproduction and development by mediating Dio3os in mouse endometrial stromal cells

Xie

Wang

et al. 2019

J Biochem & Molecular Tox

Self Cite

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Zearalenone (ZEA) and imprinted long noncoding RNAs (lncRNAs) are both closely related to reproduction and development. However, whether they have connections in regulating reproduction and development is not clear yet. The aim of this research is to investigate their relationship. lncRNA microarray was performed to analyze differentially expressed genes, and real-time quantitative polymerase chain reaction (PCR) was used to verify the accuracy of microarray analysis. Meanwhile, the technologies of rapid amplification of cDNA ends, RNA fluorescence in situ hybridization and bioinformatics were adopted to characterize the selected lncRNA. Analysis of lncRNA microarray showed lncRNAs and messenger RNAs related to reproduction and development were significantly differently expressed, and Dio3os was probably the target lncRNA. Then, the experiment of real-time quantitative PCR verified the accuracy of microarray data. Characterization of Dio3os showed Dio3os, an antisense lncRNA with 2312 bp and 15 open reading frames, was enriched in the cytoplasm. Our findings suggest ZEA probably exerts toxic effects on reproduction and development by mediating Dio3os. Highlights 1. Lots of long noncoding RNAs (lncRNAs) are also important in reproduction and development, and Dio3os is one of them. 2. Zearalenone probably exerts toxic effects on reproduction and development by mediating Dio3os at the genetic level. 3. Dio3os may be a lncRNA related to reproduction and development, and it probably works by regulating Dio3. K E Y W O R D S Dio3os, fluorescence in situ hybridization, lncRNA microarray, rapid amplification of cDNA ends, zearalenone (ZEA)

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Exploration of ZEA cytotoxicity to mouse endometrial stromal cells and RNA-seq analysis

Cited by 8 publications

References 37 publications

Mycotoxin zearalenone exposure impairs genomic stability of swine follicular granulosa cells in vitro

Mycotoxin zearalenone exposure impairs genomic stability of swine follicular granulosa cells in vitro

Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review

ZEA exerts toxic effects on reproduction and development by mediating Dio3os in mouse endometrial stromal cells

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