Embryotoxicity of methylparaben to zebrafish (Danio rerio) early-life stages

Merola, Carmine; Perugini, Monia; Conte, Annamaria; Angelozzi, Giovanni; Bozzelli, M.; Amorena, Michele

doi:10.1016/j.cbpc.2020.108792

Cited by 28 publications

(14 citation statements)

References 52 publications

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“…Recently, several experimental studies have investigated the embryonic toxicity of parabens using zebrafish larvae providing several lines of evidence, for the detrimental effects of parabens on zebrafish early-life stages with attention to its developmental toxicity [ 21 , 22 ]. Observed features among zebrafish larvae where pericardial edema, yolk edema, blood stasis, reduction in blood circulation, reduced heartbeat and notochord curvature [ 23 ]. While parabens are commonly found in personal care products such as hair spray, it is unclear, whether the maternal use during the periconceptional period might exert toxic effects on human embryonic development.…”

Section: Discussionmentioning

confidence: 99%

Parental risk factors for congenital diaphragmatic hernia – a large German case-control study

et al. 2021

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Background Evidence for periconceptional or prenatal environmental risk factors for the development of congenital diaphragmatic hernia (CDH) is still scarce. Here, in a case-control study we investigated potential environmental risk factors in 199 CDH patients compared to 597 healthy control newborns. Methods The following data was collected: time of conception and birth, maternal BMI, parental risk factors such as smoking, alcohol or drug intake, use of hairspray, contact to animals and parental chronic diseases. CDH patients were born between 2001 and 2019, all healthy control newborns were born in 2011. Patients and control newborns were matched in the ratio of three to one. Results Presence of CDH was significantly associated with maternal periconceptional alcohol intake (odds ratio = 1.639, 95% confidence interval 1.101–2.440, p = 0.015) and maternal periconceptional use of hairspray (odds ratio = 2.072, 95% confidence interval 1.330–3.229, p = 0.001). Conclusion Our study suggests an association between CDH and periconceptional maternal alcohol intake and periconceptional maternal use of hairspray. Besides the identification of novel and confirmation of previously described parental risk factors, our study underlines the multifactorial background of isolated CDH.

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Section: Discussionmentioning

confidence: 99%

Parental risk factors for congenital diaphragmatic hernia – a large German case-control study

et al. 2021

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“…Parabens were tested at following concentrations: BuP 5, 50 and 500 μg/L; EtP 50, 500 and 5000 μg/L; MeP 100, 1000 and 10,000 μg/L. Tested concentrations were selected from previous fish embryo acute toxicity (FET) tests, including concentrations of exposure that did not induce lethal and sublethal alterations (Merola, Lai, et al, 2020; Merola, Perugini, et al, 2020). Moreover, the lowest concentrations of exposure included a range of environmentally realistic concentrations.…”

Section: Methodsmentioning

confidence: 99%

“…Their use, especially at early‐life stages before independent feeding, aligns with principles of 3Rs (Replacement, Reduction and Refinement) and further enjoys the advantages of scaled‐down research infrastructures, easy manipulation and cost effectiveness, allowing the application to large‐scale screening of chemical compounds via high‐throughput automated behavioural systems (Basnet et al, 2019). Recent studies provided initial evidence that exposure to sublethal doses of parabens, included BuP, EtP and MeP, induces developmental alterations in zebrafish larvae (Bereketoglu & Pradhan, 2019;Merola, Lai, et al, 2020; Merola, Perugini, et al, 2020). For example, Merola and colleagues (Merola, Lai, et al, 2020; Merola, Perugini, et al, 2020) reported that larvae exposed to 1 and 2.5 mg/L of BuP, 5, 10, 20 and 30 mg/L of EtP, or 10, 30, 60 and 80 mg/L of MeP displayed alterations such as reduced heartbeat, reduced blood circulation, blood stasis, pericardial oedema, yolk oedema, misshaped yolk sac and deformed notochord.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies provided initial evidence that exposure to sublethal doses of parabens, included BuP, EtP and MeP, induces developmental alterations in zebrafish larvae (Bereketoglu & Pradhan, 2019;Merola, Lai, et al, 2020; Merola, Perugini, et al, 2020). For example, Merola and colleagues (Merola, Lai, et al, 2020; Merola, Perugini, et al, 2020) reported that larvae exposed to 1 and 2.5 mg/L of BuP, 5, 10, 20 and 30 mg/L of EtP, or 10, 30, 60 and 80 mg/L of MeP displayed alterations such as reduced heartbeat, reduced blood circulation, blood stasis, pericardial oedema, yolk oedema, misshaped yolk sac and deformed notochord.…”

Section: Introductionmentioning

confidence: 99%

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Behavioural effects of early‐life exposure to parabens in zebrafish larvae

Merola

Lucon‐Xiccato

Bertolucci

et al. 2021

J of Applied Toxicology

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Parabens are classified as endocrine disrupting chemicals due to their ability to activate several nuclear receptors causing changes in hormones‐dependent signalling pathways. Central nervous system of developing organisms is particularly vulnerable to changes in hormonal pathways, which could lead to altered brain function, abnormal behaviour and even diseases later in life. The aim of the present study was to investigate the effects of exposure to butylparaben (BuP), ethylparaben (EtP) and methylparaben (MeP) during early development on nervous system using zebrafish larvae's behavioural models. Zebrafish were exposed until 4 days post fertilization (dpf) to three concentrations of each paraben chosen considering the environmentally realistic concentrations of human exposure and the benchmark‐dose lower bound calculated for zebrafish larvae (BuP: 5, 50 and 500 μg/L; EtP: 50, 500 and 5000 μg/L; MeP: 100, 1000 and 10,000 μg/L). Activity in novel and in familiar environment, thigmotaxis, visual startle response and photic synchronization of the behavioural circadian rhythms were analysed at 4, 5 and 6 dpf. Zebrafish larvae exposed to BuP 500 μg/L and EtP 5000 μg/L revealed increased anxiety‐like behaviour in novel environment. Larvae treated with 500 μg/L of BuP showed reduced activity in familiar and marginally in unfamiliar environment, and larvae exposed to 5000 μg/L of EtP exhibited hyperactivity in familiar environment. Parabens exposure did not influence the visual startle response and the photic synchronization of circadian rhythms in zebrafish larvae. This research highlighted as the exposure to parabens has the potential to interfere with behavioural development of zebrafish.

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“…Previous studies have shown that parabens can induce diverse adverse biological effects, including endocrine activity, carcinogenesis, infertility, spermatogenesis disturbance, adipogenesis, perinatal exposure impact, and ecologic effects . In concern of developmental toxicity, MeP exposure induced the pericardial edema (PE), yolk edema, and notochord curvature in zebrafish embryo . EtP exposure prolonged the development cycle of Drosophila melanogaster, leading to the delay of the hormone secretion peak .…”

Section: Introductionmentioning

confidence: 99%

Assessment of Thyroid Endocrine Disruption Effects of Parabens Using In Vivo, In Vitro, and In Silico Approaches

Liang

Yang

Liu

et al. 2021

Environ. Sci. Technol.

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The extensive applications of parabens in foods, drugs, and cosmetics cause inevitable exposure to humans. Revealing the developmental toxicity of parabens is of utmost importance regarding their safety evaluation. In this study, the effects of four commonly used parabens, including methyl paraben (20 ∼ 200 μM), ethyl paraben (20 ∼ 100 μM), propyl paraben (5 ∼ 20 μM), and butyl paraben (BuP, 2 ∼ 10 μM), were investigated on the early development of zebrafish embryos and larvae. The underlying mechanisms were explored from the aspect of their disturbance in the thyroid endocrine system using in vivo, in vitro, and in silico assays. Paraben exposure caused deleterious effects on the early development of zebrafish, with BuP displaying the highest toxicity among all, resulting in the exposure concentration-related mortality, decreased hatching rate, reduced body length, lowered heart rate, and the incidence of malformation. Further investigation showed that paraben exposure reduced thyroid hormone levels and disturbed the transcriptional expressions of the target genes in the hypothalamic–pituitary–thyroid axis. Molecular docking analysis combined with in vitro GH3 cell proliferation assay testified that all test parabens exhibited thyroid receptor agonistic activities. The findings confirmed the developmental toxicity of the test parabens and their thyroid endocrine disruption effects, providing substantial evidence on the safety control of paraben-based preservatives.

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Embryotoxicity of methylparaben to zebrafish (Danio rerio) early-life stages

Cited by 28 publications

References 52 publications

Parental risk factors for congenital diaphragmatic hernia – a large German case-control study

Parental risk factors for congenital diaphragmatic hernia – a large German case-control study

Behavioural effects of early‐life exposure to parabens in zebrafish larvae

Assessment of Thyroid Endocrine Disruption Effects of Parabens Using In Vivo, In Vitro, and In Silico Approaches

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