Di-2-ethylhexyl phthalate induces heart looping disorders during zebrafish development

Sun, Yinghao; Yang, Fan; Liu, Yang; Ming, Yu; Wu, Feng; Wang, Guokun

doi:10.1177/07482337211019184

Cited by 12 publications

(5 citation statements)

References 29 publications

(27 reference statements)

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“…These indicated that fetal hyperglycemia and DEHP exposure in zebrafish embryos can cause developmental anomalies. In accordance with the pericardial edema observed in the DEHP exposed embryos, Sun et al (2021) also reported that DEHP induced heart looping disorders and pericardial edema during zebrafish development. The expression of transcription factors regulating heart development were also shown to be affected by DEHP, which may be related to disruption of heart development (Sun et al, 2021).…”

Section: Discussionsupporting

confidence: 78%

Diethylhexyl phthalate exposure amplifies oxidant and inflammatory response in fetal hyperglycemia model predisposing insulin resistance in zebrafish embryos

Kaplan,

Beler,

Ünal

et al. 2024

Toxicol Ind Health

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Exposure of zebrafish embryos to glucose is a suitable model for the fetal hyperglycemia seen in gestational diabetes. Diethylhexyl phthalate (DEHP), which is considered an endocrine-disrupting chemical, is one of the most common phthalate derivatives used in stretching plastic and is encountered in every area where plastic is used in daily life. In the present study, the effects of DEHP on pathways related to insulin resistance and obesity were examined in zebrafish embryos exposed to glucose as a fetal hyperglycemia model. Zebrafish embryos were exposed to DEHP, glucose, and glucose + DEHP for 72 h post-fertilization (hpf), and developmental parameters and locomotor activities were monitored. At 72 hpf ins, lepa, pparγ, atf4a, and il-6 expressions were determined by RT-PCR. Glucose, lipid peroxidation (LPO), nitric oxide (NO) levels, glutathione S-transferase (GST), superoxide dismutase (SOD), and acetylcholine esterase (AChE) activities were measured spectrophotometrically. Compared with the control group, glucose, LPO, GST activity, il6, and atf4a expressions increased in all exposure groups, while body length, locomotor, and SOD activities decreased. While AChE activity decreased in the DEHP and glucose groups, it increased in the glucose + DEHP group. Although glucose exposure increased pparγ and lepa expressions, DEHP significantly decreased the expressions of pparγ and lepa both in the DEHP and glucose + DEHP groups. Our findings showed that DEHP amplified oxidant and inflammatory responses in this fetal hyperglycemia model, predisposing insulin resistance in zebrafish embryos.

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Section: Discussionsupporting

confidence: 78%

Diethylhexyl phthalate exposure amplifies oxidant and inflammatory response in fetal hyperglycemia model predisposing insulin resistance in zebrafish embryos

Kaplan,

Beler,

Ünal

et al. 2024

Toxicol Ind Health

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“…In mice, maternal exposure to diethylhexyl phthalate (DEHP) caused cardiac developmental defects [ 25 , 202 ]. Work in zebrafish yielded similar findings, where exposure to DEHP [ 203 ], butyl benzyl phthalate (BBP) [ 204 ], or dibutyl phthalate (DBP) [ 205 ] during development led to cardiac developmental defects. However, whether there are sex differences in phthalate-induced developmental defects is unclear.…”

Section: Introductionmentioning

confidence: 95%

Developmental toxicant exposures and sex-specific effects on epigenetic programming and cardiovascular health across generations

Svoboda

Ishikawa

Dolinoy

2022

Environmental Epigenetics

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Despite substantial strides in diagnosis and treatment, cardiovascular diseases (CVDs) continue to represent the leading cause of death in the US and around the world, resulting in significant morbidity and loss of productive years of life. It is increasingly evident that environmental exposures during early development can influence CVD risk across the life course. CVDs exhibit marked sexual dimorphism, but how sex interacts with environmental exposures to affect cardiovascular health is a critical and understudied area of environmental health. Emerging evidence suggests that developmental exposures may have multi- and transgenerational effects on cardiovascular health, with potential sex differences; however, further research in this important area is urgently needed. Lead (Pb), phthalate plasticizers, and perfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with numerous adverse human health effects. Notably, recent evidence suggests that developmental exposure to each of these toxicants has sex-specific effects on cardiovascular outcomes, but the underlying mechanisms, and their effects on future generations, require further investigation. This Review Article will highlight the role for the developmental environment in influencing cardiovascular health across generations, with a particular emphasis on sex differences and epigenetic mechanisms In particular, we will focus on the current evidence for adverse multi and transgenerational effects of developmental exposures to Pb, phthalates, and PFAS, and highlight areas where further research is needed.

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“…The mechanism underlying the effect of DEHP on Desmin levels was explained by Tang et al ( 2018 ) and Sun et al ( 2021 ). They stated that DEHP can down regulate GATA4 expression, which is a key transcriptional factor in cardiac development and controls the expression of Desmin protein in the heart.…”

Section: Discussionmentioning

confidence: 97%

Granulocyte-colony stimulating factor ameliorates di-ethylhexyl phthalate-induced cardiac muscle injury via stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms

et al. 2023

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Phthalates are common plasticizers present in medical-grade plastics and other everyday products. Di-ethylhexyl phthalate (DEHP) has been noted as a causative risk factor for the initiation and augmentation of cardiovascular functional disorders. G-CSF is a glycoprotein found in numerous tissues throughout the body and is currently applied in clinical practice and has been tested in congestive heart failure. We aimed to examine in depth the effect of DEHP on the histological and biochemical structure of the cardiac muscle in adult male albino rats and the mechanisms underlying the possible ameliorative effect of G-CSF. Forty-eight adult male albino rats were divided into control group, DEHP group, DEHP+ G-CSF group and DEHP-recovery group. We measured serum levels of aspartate aminotransferase (AST), creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Left ventricular sections were processed for light and electron microscope examination, and immunohistochemical staining of Desmin, activated Caspase-3 and CD34. DEHP significantly increased enzyme levels, markedly distorted the normal architecture of cardiac muscle fibers, downregulated Desmin protein levels and enhanced fibrosis, and apoptosis. G-CSF treatment significantly decreased the enzyme levels compared to DEHP group. It enhanced CD34 positive stem cells recruitment to injured cardiac muscle, therefore improved the ultrastructural features of most cardiac muscle fibers via anti-fibrotic and anti-apoptotic effects in addition to increased Desmin protein expression levels. The recovery group showed partial improvement due to persistent DEHP effect. In conclusion, administration of G-CSF effectively corrected the histopathological, immunohistochemical and biochemical alterations in the cardiac muscle after DEHP administration by stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms.

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Di-2-ethylhexyl phthalate induces heart looping disorders during zebrafish development

Cited by 12 publications

References 29 publications

Diethylhexyl phthalate exposure amplifies oxidant and inflammatory response in fetal hyperglycemia model predisposing insulin resistance in zebrafish embryos

Diethylhexyl phthalate exposure amplifies oxidant and inflammatory response in fetal hyperglycemia model predisposing insulin resistance in zebrafish embryos

Developmental toxicant exposures and sex-specific effects on epigenetic programming and cardiovascular health across generations

Granulocyte-colony stimulating factor ameliorates di-ethylhexyl phthalate-induced cardiac muscle injury via stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms

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