Cadmium significantly changes major morphometrical points and cardiovascular functional parameters during early development of zebrafish

Mitovic, Nikola; Maksimovic, Stefan; Puflović, Darko; Kovačević, Sanjin; Lopičić, Srdjan; Todorović, Jovan; Spasić, Svetolik; Dinčić, Marko; Ostojic, Jelena Nesovic

doi:10.1016/j.etap.2021.103723

Cited by 10 publications

(4 citation statements)

References 71 publications

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“…50,93 Apoptosis induced by toxicants is the potential reason for structural changes in the eye of zebrash. 61 During eye development, apoptotic death of the eye occurs through the casp3 gene regulation pathway. 77 Relative gene expression of casp-3 was downregulated which indicates that CP-toxicity inactivated the caspase cascade regulation which might affect the normal development of eye.…”

Section: Discussionmentioning

confidence: 99%

“…60 The decrease in the heart rate is an indication of a compensatory mechanism to a toxicant. 61 Abnormal heart beats could have an impact on endothelial vessels which supply the yolk sac, and this could possibly lead to yolk sac oedema. 9 Drug-induced apoptosis in the pericardial space and oxidative stress-mediated damage of cardiomyocytes and vascular endothelial cells could affect the cardiac system of zebrafish embryos.…”

Section: Discussionmentioning

confidence: 99%

“…Scientifically it was proved that chemicals (including drugs) caused developmental irregularities (weight, growth, 61 eye impairments, 100 and oxidative stress 17,79 ) were often consistent with adult zebrafish or mammalian models or humans. CP-induced changes in early developmental stages which might also have relevance to CP-administered infants and children, need to be clarified.…”

Section: Discussionmentioning

confidence: 99%

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Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish

Hema¹,

Krishnan²,

Ramesh³

et al. 2023

Environ. Sci.: Processes Impacts

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish

Hema¹,

Krishnan²,

Ramesh³

et al. 2023

Environ. Sci.: Processes Impacts

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“… 20 Other mouse models have demonstrated that maternal/prenatal Cd exposure caused differential expression of genes and pathways associated with heart development and hypertension in the hearts of newborns 21 and altered the expression of genes that affect cardiomyocyte proliferation and differentiation, including GATA4 . 22 Zebrafish exposed to Cd during development had significantly lower heart rates during development 23 and as adults. 24 In a group of Chinese patients, maternal exposure to Cd was a significant risk factor for CHDs in the offspring.…”

Section: Introductionmentioning

confidence: 96%

Cardiac Development in the Presence of Cadmium: An in Vitro Study Using Human Embryonic Stem Cells and Cardiac Organoids

Chen

Luz

et al. 2022

Environ Health Perspect

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Background: Exposure to cadmium (Cd) is associated with cardiovascular diseases. Maternal Cd exposure is a significant risk factor for congenital heart disease. However, mechanisms of Cd on developmental cardiotoxicity are not well defined. Objectives: We evaluated the effects of Cd on the different stages (mesoderm, cardiac induction, cardiac function) of cardiac development using an early embryo development in vitro model and two- or three-dimensional (2- or 3D) cardiomyocyte and cardiac organoid formation models mimicking early cardiac development. Methods: Embryonic stem cells (ESCs) form 3D aggregates, called embryoid bodies, that recapitulate events involved with early embryogenesis (e.g., germ layer formation). This model was used for early germ layer formation and signaling pathway identification. The 2D cardiomyocyte differentiation from the human ESCs model was used to explore the effects of Cd exposure on cardiomyocyte formation and to model mesoderm differentiation and cardiac induction, allowing us to explore different developmental windows of Cd toxicity. The 3D cardiac organoid model was used in evaluating the effects of Cd exposure on contractility and cardiac development. Results: Cd ( ; ) lowered the differentiation of embryoid bodies to mesoderm via suppression of –signaling pathways. During early mesoderm induction, the mesoderm-associated transcription factors MESP1 and EOMES showed a transient up-regulation, which decreased later in the cardiac induction stage. Cd ( ) lowered mesoderm formation and cardiac induction through suppression of the transcription factors and mesoderm marker genes HAND1 , SNAI2 , HOPX , and the cardiac-specific genes NKX2 -5, GATA4 , troponin T, and . In addition, Cd-induced histone modifications for both gene activation (H3K4me3) and repression (H3K27me3), which play vital roles in regulating mesoderm commitment markers. The effects of Cd inhibition on cardiomyocyte differentiation were confirmed in 3D cardiac organoids. Discussion: In conclusion, using a human ESC-derived 2D/3D in vitro differentiation model system and cardiac organoids, we demonstrated that low-dose Cd suppressed mesoderm formation through mesoderm gene histone modification, thus inhibiting cardiomyocyte differentiation and cardiac induction. The studies provide valuable insights into cellular events and molecular mechanisms associated with Cd-induced congenital heart disease. https://doi.org/10.1289/EHP11208

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Environmental risk of titanium dioxide nanoparticle and cadmium mixture: developmental toxicity assessment in zebrafish (Danio rerio)

et al. 2022

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Cadmium significantly changes major morphometrical points and cardiovascular functional parameters during early development of zebrafish

Cited by 10 publications

References 71 publications

Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish

Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish

Cardiac Development in the Presence of Cadmium: An in Vitro Study Using Human Embryonic Stem Cells and Cardiac Organoids

Environmental risk of titanium dioxide nanoparticle and cadmium mixture: developmental toxicity assessment in zebrafish (Danio rerio)

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