RNA-seq analysis of testes from flurochloridone-treated rats

Zhou, Shanshan; Li, Rui; Hou, Wanwan; Wang, Yue; Zhang, Suhui; Yu, Ying; Zhang, Lei; Zhu, Hongyan; Zhang, Zhichao; Fang, Jing; Chang, Xiuli; Zhang, Yubin; Liu, Luqing; Tang, Liming; Zhou, Zhijun

doi:10.1080/15376516.2019.1701593

Cited by 3 publications

(2 citation statements)

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“…The impair of herbicides on male reproduction and testicular toxicity has been concerned [30][31][32] and many studies focus on Sertoli cells since they are crucial important for homeostasis of testis by establishing blood-testis barrier and secreting active substance [10]. As a novel herbicide, FLC has been widely used in many countries and studies have shown that the target cell of FLC may be Sertoli cell for it can induce ROS cumulative damage [17,18,33], and disturb calcium homeostasis [16], which suggests the possible occurrence of ER stress [34]. In this study, the role of ER stress in FLC-induced apoptosis of mouse TM4 Sertoli cells was explored.…”

Section: Discussionmentioning

confidence: 99%

Flurochloridone Induced Cell Apoptosis via ER Stress and eIF2α-ATF4/ATF6-CHOP-Bim/Bax Signaling Pathways in Mouse TM4 Sertoli Cells

Zhang

Zhao

et al. 2022

IJERPH

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Flurochloridone (FLC), as a novel herbicide, has been widely used in many countries since 1980s. Current studies have shown that FLC has toxic effects on male reproduction and its target organ is testis, while the underlying mechanism is still unknown. Mouse testis Sertoli cell line TM4 cells were used as an in vitro model and treated with FLC at different doses (40, 80, 160 μM) for different times (6, 12, 24 h). Cell viability, cytotoxicity and apoptotic cells were detected by CCK-8 assay, LDH leakage assay and flow cytometry. The protein levels of GRP78, phosphorylated-eIF2α, ATF4, ATF6, CHOP, Bim and Bax were observed by Western Blot and Immunofluorescence staining. FLC inhibited cell viability and induced cytotoxicity in dose-dependent way in TM4 cells. The percentage of apoptotic cells were 6.2% ± 0.6%, 7.3% ± 0.3%, 9.8% ± 0.4%, 13.2% ± 0.2%, respectively. The expression levels of ER stress and UPR related proteins were activated over dose. Meanwhile, the pro-apoptotic proteins (Bim and Bax) were also up-regulated in dose-dependent. After pretreated with ISRIB, the inhibitor of eIF2α phosphorylation, the elevated expression of GRP78, phosphorylated-eIF2α, ATF4, ATF6, CHOP and Bim was down to normal level accordingly. In conclusion, FLC induced apoptosis in TM4 cells mediated by UPR signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Flurochloridone Induced Cell Apoptosis via ER Stress and eIF2α-ATF4/ATF6-CHOP-Bim/Bax Signaling Pathways in Mouse TM4 Sertoli Cells

Zhang

Zhao

et al. 2022

IJERPH

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“…Transgenerational epimutations of primordial germ cells were observed following exposure to vinclozolin fungicide [56]. Insecticide and herbicide compounds have shown similar endocrine disruption activities in the testes [57,58]. In epidemiological studies, no clear association between elevated maternal serum concentrations of hexachlorobenzene fungicide and TGCT risk has been found so far [59,60], while increased risks were observed for p,p'-dichlorodiphenyldichloroethylene and chlordane organochlorine insecticides; although serum was collected around son's diagnosis [59,61,62].…”

Section: Use Of Insecticides On Other Animals Ementioning

confidence: 99%

Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study

et al. 2021

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Background Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. Methods We conducted a case-control study of 304 TGCT cases, aged 18–45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants’ mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son’s birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80–2.01) or herbicides (OR = 1.15, CI = 0.67–2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04–2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26–4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06–5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12–3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. Conclusions Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.

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High doses of clethodim-based herbicide GrassOut Max poses reproductive hazard by affecting male reproductive function and early embryogenesis in Swiss albino mice

Dcunha,

Kumari,

Najar

et al. 2023

Chemosphere

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RNA-seq analysis of testes from flurochloridone-treated rats

Cited by 3 publications

References 36 publications

Flurochloridone Induced Cell Apoptosis via ER Stress and eIF2α-ATF4/ATF6-CHOP-Bim/Bax Signaling Pathways in Mouse TM4 Sertoli Cells

Flurochloridone Induced Cell Apoptosis via ER Stress and eIF2α-ATF4/ATF6-CHOP-Bim/Bax Signaling Pathways in Mouse TM4 Sertoli Cells

Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study

High doses of clethodim-based herbicide GrassOut Max poses reproductive hazard by affecting male reproductive function and early embryogenesis in Swiss albino mice

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