The fungicide mancozeb induces toxic effects on mammalian granulosa cells

Paro, Rita; Tiboni, Gian Mario; Buccione, Roberto; Rossi, Gianna; Cellini, Valerio; Canipari, Rita; Cecconi, Sandra

doi:10.1016/j.taap.2012.02.005

Cited by 69 publications

(43 citation statements)

References 33 publications

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“…Previous studies showed that mancozeb can exert its pro-apoptotic ability on lymphocytes [45], mononuclear cells [46] and neurocytes [47]. More notably, mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of apoptotic features [12]. In this study, we indeed observed apoptosis in both granulosa cells and oocytes, while, resveratrol could reduce the frequency of the apoptotic events.…”

Section: Discussionsupporting

confidence: 69%

“…Furthermore, mancozeb could affects female fertility either by targeting the hypothalamo-hypophysial-ovarian axis [8] or inducing a direct cytotoxicity on oocytes [9, 10], embryo [11] and granulosa cells [12]. A previous report has shown a strong relationship between mancozeb exposure and increased incidence of thyroid disease in female spouses of pesticide applicators.…”

Section: Introductionmentioning

confidence: 99%

“…As regards mancozeb cytotoxic effects, previous research studies suggested that it mancozeb may induce a reduction of mouse fertilization rate together with alterations of oocyte meiotic spindle morphology, impaired mouse embryo development and blastomere apoptosis induction [10, 16]. Moreover, mancozeb induces dose-dependent morphological modifications and substantial alteration of p53 pathway in both mouse and human granulosa cells [12]. These previous studies supported that mancozeb is toxic to fertility, but most of these studies were based on in vitro or acute exposure observation and the mechanisms of toxicity are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes

Liu

Wang

et al. 2016

Oncotarget

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Mancozeb, a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Mancozeb could lead to mitochondria dysfunction, cellular anti-oxidation enzymes depletion and apoptotic pathways activation. Previous studies indicated the exposure of mancozeb through mother would lead to irregular estrous cycles, decreased progesterone levels, reduced litter sizes, and more frequent delivery of dead fetuses. In this study, we investigated mancozeb inducing reproductive toxicity, especially focusing on its apoptotic effect and epigenetic modifications. We also showed that resveratrol, a kind of phytoalexin found in peanuts and grapes, can alleviate mancozeb's adverse effects, such as declined fertility, decreased ovary weight and primary follicles. Besides, mancozeb treated oocytes displayed suboptimal developmental competence and this can also be improved by treatment of resveratrol. More detailed investigation of these processes revealed that mancozeb increased reactive oxygen species, causing cell apoptosis and abnormal epigenetic modifications, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can alleviate mancozeb induced infertility and this was mainly through the correction of apoptotic tendency and the abnormity of cellular epigenetic modification.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes

Liu

Wang

et al. 2016

Oncotarget

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“…As confirmed by recent studies, mancozeb exposure is a risk factor for spontaneous abortion, maternal mortality, and fetal malformations in rat and rabbit experimental models [21]. Moreover, it is strongly linked to teratogenic, mutagenic, and carcinogenic risks [24] because of its ability to induce genotoxic and malignant alterations in human ovarian cells [21,25,26].…”

Section: Introductionmentioning

confidence: 92%

“…Paro et al showed how increasing concentrations of mancozeb (0.001-1 µg/mL) induce alterations in morphology and migration patterns in mouse granulosa cells, with a reduction in p53 expression levels [25]. Human granulosa cells, derived from women who underwent assisted reproductive therapy, when exposed to increasing mancozeb concentrations, showed alteration in p53 levels and morphology changes.…”

Section: In Vitro Experimental Studiesmentioning

confidence: 99%

Association between Female Reproductive Health and Mancozeb: Systematic Review of Experimental Models

Bianchi

Nottola

Torge

et al. 2020

IJERPH

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Mancozeb is a widely used fungicide approved for use in agriculture in many countries with long persistence in the environment and consequent bioaccumulation in tissues and biological fluids. Despite the large amount of studies published in recent years, the relationship between mancozeb exposure and female reproductive health is not fully elucidated. In order to summarize current evidence on mancozeb exposure and female reproductive disease, we performed a systematic review of literature. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to make this review. An adapted version of the National Toxicology Program's Office of Health and Assessment and Translation (OHAT) framework was used to evaluate the risk of bias. Electronic search on two databases (PubMed and Scopus) was used to find experimental studies (in vitro and in vivo) on mancozeb exposure. The database search identified 250 scientific articles, 20 of which met our inclusion criteria. Selected data were then reviewed and summarized in tables. Overall, mancozeb represents a hazard for female reproductive health, with different mechanisms of action. Undoubtedly more experimental and epidemiological studies are required to definitively validate mancozeb as reproductive toxicant.

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Ameliorative potential of vitamin C and E against Roundup‐glyphosate induced genotoxicity triggering apoptosis in caprine granulosa cells

Bhardwaj

Mittal

Saraf

et al. 2022

Environ and Mol Mutagen

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The present study was aimed to investigate the genotoxic and apoptotic effects of glyphosate (GLP) in Roundup formulation along with mitigation of two potent antioxidants that is, vitamin C and E in caprine granulosa cells in vitro. The entire work was done in a dose and time dependent manner where different concentrations of GLP (0.1, 2.0, and 4.0 mg/ml) in Roundup and antioxidants (0.5 and 1.0 mM) were employed to culture of granulosa cells for exposure durations of 24, 48, and 72 h. Analysis of GLP‐induced geno‐toxicity was accomplished by using single cell gel electrophoresis (comet assay) assay. Results have shown increased incidences of DNA fragmentation, evidenced by presence of different types of comets (Type 1–Type 4) in Roundup‐GLP‐ exposed groups in contrast to the control group (Type 0 comet). However, mitigation by both vitamin C and E was significant (p < .05) in combating the GLP‐induced genotoxicity in granulosa cells in a concentration‐ and time‐dependent manner. The results of our study provide a clear indication of the ameliorative actions of vitamin C and E against Roundup‐GLP‐induced genotoxicity that instigate apoptosis in ovarian granulosa cells of caprine.

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The fungicide mancozeb induces toxic effects on mammalian granulosa cells

Cited by 69 publications

References 33 publications

Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes

Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes

Association between Female Reproductive Health and Mancozeb: Systematic Review of Experimental Models

Ameliorative potential of vitamin C and E against Roundup‐glyphosate induced genotoxicity triggering apoptosis in caprine granulosa cells

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