Prenatal lead acetate exposure induces apoptosis and changes GFAP expression during spinal cord development

Müller, Yara Maria Rauh; Kobus, Karoline; Schatz, Janaína Chaves; Ammar, Dib; Nazari, Evelise Maria

doi:10.1016/j.ecoenv.2011.08.004

Cited by 12 publications

(7 citation statements)

References 42 publications

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“…GFAP is expressed almost exclusively in astrocytes within the CNS, and is thought to be the hallmark of astrocyte differentiation (Bignami et al, ; Radin et al, ; Valles et al, ). This astroglia protein provides the structural support for neurons and is crucial for neuronal morphogenesis and the formation of stable astrocytic processes in the brain (Dutra et al, ; Muller et al, ). Therefore, alterations in GFAP protein expression is a particularly attractive mechanism for explaining the deleterious effect of prenatal exposure to EtOH on astrocytes and, consequently, on different aspects of CNS development, including neuronal migration and myelination that have been shown to be affected in cells, animals, and human exposed to EtOH (Jones et al, ; Ikonomidou et al, ; Tateno et al, ; Anthony et al, ; Camarillo and Miranda, ; Thomas et al, ; Krishnamoorthy et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Ethanol Alters Proliferation and Differentiation of Normal and Chromosomally Abnormal Human Embryonic Stem Cell‐Derived Neurospheres

Krishnamoorthy

Gerwe

Scharer

et al. 2013

Birth Defects Research Pt B

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Ethanol is a powerful substance and, when consumed during pregnancy, has significant psychoactive and developmental effects on the developing fetus. These abnormalities include growth retardation, neurological deficits, and behavioral and cognitive deficiencies, commonly referred to as fetal alcohol spectrum disorder. The effect of ethanol has been reported to affect cellular development on the embryonic level, however, not much is known about mutations contributing to the influence of ethanol. The purpose of our study was to determine if mutation contribute to changes in differentiation patterning, cell-cycle regulatory gene expression, and DNA methylation in human embryonic stem cells after ethanol exposure. We exposed human embryonic stem cells (with and without know DNA mutations) to a low concentration (20 mM) of ethanol and measured neurosphere proliferation and differentiation, glial protein levels, expression of various cell-cycle genes, and DNA methylation. Ethanol altered cell-cycle gene expression between the two cell lines; however, gene methylation was not affected in ether lines.

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Section: Discussionmentioning

confidence: 99%

Ethanol Alters Proliferation and Differentiation of Normal and Chromosomally Abnormal Human Embryonic Stem Cell‐Derived Neurospheres

Krishnamoorthy

Gerwe

Scharer

et al. 2013

Birth Defects Research Pt B

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“…In fact, in ovo development is a good model for toxicity studies because embryos develop in the absence of maternal factors, which may compromise the assay results. The metal injection in the yolk sac is effective for neurodevelopmental toxicology, and these assays have been validated in our previous studies with lead acetate and MeHg [ 23 , 28 , 31 ]. Moreover, the experimental design is also important, particularly the establishment of the exposure time.…”

Section: Discussionmentioning

confidence: 99%

“…Next, the spinal cord sections ( n = 7 embryos per group of three independent experiments) were washed with tap water and counterstained with hematoxylin. Mercury deposition was evaluated as brown stained cells, which represent silver surrounding the deposited mercury [ 27 ], and classified as absent (−), mild (+), moderate (++), and intense (+++) by an investigator who was blind to the treatment assignments according to Müller et al [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

MeHg Developing Exposure Causes DNA Double-Strand Breaks and Elicits Cell Cycle Arrest in Spinal Cord Cells

Ferreira

Ammar

Bourckhardt

et al. 2015

Journal of Toxicology

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The neurotoxicity caused by methylmercury (MeHg) is well documented; however, the developmental neurotoxicity in spinal cord is still not fully understood. Here we investigated whether MeHg affects the spinal cord layers development. Chicken embryos at E3 were treated in ovo with 0.1 μg MeHg/50 μL saline solution and analyzed at E10. Thus, we performed immunostaining using anti-γ-H2A.X to recognize DNA double-strand breaks and antiphosphohistone H3, anti-p21, and anti-cyclin E to identify cells in proliferation and cell cycle proteins. Also, to identify neuronal cells, we used anti-NeuN and anti-βIII-tubulin antibodies. After the MeHg treatment, we observed the increase on γ-H2A.X in response to DNA damage. MeHg caused a decrease in the proliferating cells and in the thickness of spinal cord layers. Moreover, we verified that MeHg induced an increase in the number of p21-positive cells but did not change the cyclin E-positive cells. A significantly high number of TUNEL-positive cells indicating DNA fragmentation were observed in MeHg-treated embryos. Regarding the neuronal differentiation, MeHg induced a decrease in NeuN expression and did not change the expression of βIII-tubulin. These results showed that in ovo MeHg exposure alters spinal cord development by disturbing the cell proliferation and death, also interfering in early neuronal differentiation.

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“…it is well known that developmental exposure to lead is associated with embryonic toxicity or subsequent teratogenic outcomes 27,28 . Male exposure to lead increases infertility, resulting in in alterations in embryonic gene integrity in the murine model 29 .…”

Section: Discussionmentioning

confidence: 99%

In vitro estimation of metal-induced disturbance in chicken gut-oviduct chemokine circuit

Kim

Han

et al. 2019

Mol. Cell. Toxicol.

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Backgrounds:Heavy metals affect various processes in the embryonic development. embryonic fibroblasts (eFs) play key roles in the innate recognition and wound healing in reproductive tissues. Methods: Based on the relative toxicities of different inorganic metals and inorganic nonmetallic compounds against murine and chicken eF cells, mechanistic estimations were performed based on transcriptomic analyses. Results: lead (ii) acetate induced preferential injuries in the chicken eF and mechanistic analyses using transcriptome revealed that chemokine receptor-associated events are potently involved in metal-induced adverse actions. as an early sentinel of metal exposure, the precision-cut intestine slices (PCiS) induced the expression of chemokines including CXCli1 or CXCli2, which were potent gut-derived factors that activate chemokine receptors in reproductive organs after circulation. Conclusion: eF-selective metals can be estimated to trigger the chemokine circuit in the gut-reproductive axis of chickens. This in vitro methodology using PCiS-eF culture could be used as a promising alternate platform for the reproductive immunotoxicological assessment.

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Prenatal lead acetate exposure induces apoptosis and changes GFAP expression during spinal cord development

Cited by 12 publications

References 42 publications

Ethanol Alters Proliferation and Differentiation of Normal and Chromosomally Abnormal Human Embryonic Stem Cell‐Derived Neurospheres

Ethanol Alters Proliferation and Differentiation of Normal and Chromosomally Abnormal Human Embryonic Stem Cell‐Derived Neurospheres

MeHg Developing Exposure Causes DNA Double-Strand Breaks and Elicits Cell Cycle Arrest in Spinal Cord Cells

In vitro estimation of metal-induced disturbance in chicken gut-oviduct chemokine circuit

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