In utero exposure to alcohol alters cell fate decisions by hematopoietic progenitors in the bone marrow of offspring mice during neonatal development

Wang, Hao; Zhou, Huijuan; Moscatello, Kim M.; Dixon, Cheryl; Brunson, Lee Ellen; Chervenak, Robert; Chervenak, Deborah C.; Zhao, Xiangyi; Wolcott, R. Michael

doi:10.1016/j.cellimm.2006.04.002

Cited by 10 publications

(15 citation statements)

References 46 publications

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“…As an approach to studying the mechanisms by which ethanol interferes with normal patterns of differentiation we have developed an in vitro model for studying ethanol effects on the differentiation of hematopoietic progenitors. Here we report that inclusion of ethanol in liquid cultures of ONP cells, sorted from the BM of normal neonatal animals, inhibits the differentiation to the B but not to the myeloid lineage, which is in agreement with the effects observed following in utero exposure to ethanol [17]. We further show that in vitro ethanol exposure affects the expression of transcriptional regulators (EBF, Pax5) and the IL-7Rα in a manner consistent with the observed effects on differentiation.…”

Section: Introductionsupporting

confidence: 89%

“…ONP cells were sorted from bone marrow of two week-old C57BL/6J mice as previously described [17]. Cell viability was measured by staining with Trypan Blue (Sigma) and cell samples with viability of more than 98% were used for cell sorting.…”

Section: Methodsmentioning

confidence: 99%

“…Quantitative real-time PCR was performed using the Applied Biosystems Model 7700 sequence detection system (Foster City, CA). Primers and probes were designed using Primer Express Software (Applied Biosystems) and were as previously described [17]. mRNA for the transcription factors Pax5, EBF, and PU.1 and cytokine receptor IL-7Rα were quantitatively measured using GAPDH as an internal control.…”

Section: Methodsmentioning

confidence: 99%

“…In these studies we showed that neonatal animals that had been exposed to ethanol in utero had a profound decrease in B lymphocytes throughout the first few weeks of life [16,17]. B cell development occurs in discrete stages that are definable by cell morphology, molecular markers and differential expression of a number of cell surface molecules [18].…”

Section: Introductionmentioning

confidence: 99%

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Ethanol exhibits specificity in its effects on differentiation of hematopoietic progenitors

Wang¹,

Zhou²,

Chervenak³

et al. 2009

Cellular Immunology

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Ethanol is a known teratogen but the mechanisms by which this simple compound affects fetal development remain unresolved. The goal of the current study was to determine the mechanism by which ethanol affects lymphoid differentiation using an in vitro model of ethanol exposure. Primitive hematopoietic oligoclonal neonatal progenitor cells (ONP), with the phenotype Lin − HSA lo CD43 lo Sca-1 − c-Kit + that are present in neonatal but not adult bone marrow were sorted from the bone marrow of 2-week-old C57BL/6J mice and cultured under conditions that favor either B cell or myeloid cell differentiation with or without addition of ethanol. The overall growth of the ONP cells was not significantly affected by inclusion of up to 100mM ethanol in the culture medium. However, the differentiation of the progenitor cells along the B-cell pathway was significantly impaired by ethanol in a dose dependent manner. Exposure of ONP cells to 100mM ethanol resulted in greater than 95% inhibition of B cell differentiation. Conversely, ethanol concentrations up to and including 100mM had no significant effect on differentiation along the myeloid pathway. The effect of ethanol on transcription factor expression was consistent with the effects on differentiation. ONP cells grown in 100mM ethanol failed to up-regulate Pax5 and EBF, transcriptional regulators that are necessary for B cell development. However, ethanol had no significant effect on the up-regulation of PU.1, a transcription factor that, when expressed in high concentration, favors myeloid cell development. Taken together, these results suggest that ethanol has specificity in its effects on differentiation of hematopoietic progenitors.

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Section: Introductionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ethanol exhibits specificity in its effects on differentiation of hematopoietic progenitors

Wang¹,

Zhou²,

Chervenak³

et al. 2009

Cellular Immunology

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“…A continuous exposure of ETOH in a liquid diet (25% ETOH-derived calories; Dyets, Bethlehem, PA) especially prepared for experimentation in pregnant mice was used to establish our mouse model of fetal ETOH exposure (50,51). Female C57BL/6 mice were shipped from the vendor and allowed to acclimate for 1 wk.…”

Section: Methodsmentioning

confidence: 99%

Delayed neonatal lung macrophage differentiation in a mouse model of in utero ethanol exposure

Gauthier

Ping

Gabelaia

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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We have previously demonstrated that fetal ethanol exposure deranges the function and viability of the neonatal alveolar macrophage. Although altered differentiation of the alveolar macrophage contributes to pulmonary disease states within the adult lung, the effects of fetal ethanol exposure on the normal differentiation of interstitial to alveolar macrophage in the newborn lung are unknown. In the current study, using a mouse model of fetal ethanol exposure, we hypothesized that altered terminal differentiation of the neonatal interstitial to alveolar macrophage contributes to the observed cellular dysfunction in the ethanol-exposed newborn mouse. Control alveolar macrophage differentiation was characterized by increased expression of CD32/CD11b (P < or = 0.05) and increased in vitro phagocytosis of Staphylococcus aureus (P < or = 0.05) compared with interstitial macrophage. After in utero ethanol exposure, both alveolar and interstitial macrophage lacked the acquisition of CD32/CD11b (P < or = 0.05) and displayed impaired in vitro phagocytosis (P < or = 0.05). Ethanol significantly increased transforming growth factor-beta(1) (TGF-beta(1)) in the bronchoalveolar lavage fluid (P < or = 0.05), as well as in both interstitial and alveolar macrophages (P < or = 0.05). Oxidant stress contributed to the ethanol-induced changes on the interstitial and alveolar cells, since maternal supplementation with the glutathione precursor S-adenosylmethionine during ethanol ingestion normalized CD32/CD11b (P < or = 0.05), phagocytosis (P < or = 0.05), and TGF-beta(1) in the bronchoalveolar lavage fluid and macrophages (P < or = 0.05). Contrary to our hypothesis, fetal ethanol exposure did not solely impair interstitial to alveolar macrophage differentiation. Rather, fetal ethanol exposure impaired both neonatal interstitial and alveolar macrophage phagocytic function and differentiation. Increased oxidant stress and elevated TGF-beta(1) contributed to the impaired differentiation of both interstitial and alveolar macrophage.

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Mechanisms of Teratogenesis

Rouzer,

Chung,

Pinson

et al. 2023

Fetal Alcohol Spectrum Disorders

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In utero exposure to alcohol alters cell fate decisions by hematopoietic progenitors in the bone marrow of offspring mice during neonatal development

Cited by 10 publications

References 46 publications

Ethanol exhibits specificity in its effects on differentiation of hematopoietic progenitors

Ethanol exhibits specificity in its effects on differentiation of hematopoietic progenitors

Delayed neonatal lung macrophage differentiation in a mouse model of in utero ethanol exposure

Mechanisms of Teratogenesis

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