Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience.
<h4>Background</h4>In humans, ethanol exposure during pregnancy causes a spectrum of developmental defects (fetal alcohol syndrome or FAS). Individuals vary in phenotypic expression. Zebrafish embryos develop FAS-like features after ethanol exposure. In this study, we ask whether stage-s...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0020037&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850197123330473984 |
|---|---|
| author | Shaukat Ali Danielle L Champagne Alia Alia Michael K Richardson |
| author_facet | Shaukat Ali Danielle L Champagne Alia Alia Michael K Richardson |
| author_sort | Shaukat Ali |
| collection | DOAJ |
| description | <h4>Background</h4>In humans, ethanol exposure during pregnancy causes a spectrum of developmental defects (fetal alcohol syndrome or FAS). Individuals vary in phenotypic expression. Zebrafish embryos develop FAS-like features after ethanol exposure. In this study, we ask whether stage-specific effects of ethanol can be identified in the zebrafish, and if so, whether they allow the pinpointing of sensitive developmental mechanisms. We have therefore conducted the first large-scale (>1500 embryos) analysis of acute, stage-specific drug effects on zebrafish development, with a large panel of readouts.<h4>Methodology/principal findings</h4>Zebrafish embryos were raised in 96-well plates. Range-finding indicated that 10% ethanol for 1 h was suitable for an acute exposure regime. High-resolution magic-angle spinning proton magnetic resonance spectroscopy showed that this produced a transient pulse of 0.86% concentration of ethanol in the embryo within the chorion. Survivors at 5 days postfertilisation were analysed. Phenotypes ranged from normal (resilient) to severely malformed. Ethanol exposure at early stages caused high mortality (≥88%). At later stages of exposure, mortality declined and malformations developed. Pharyngeal arch hypoplasia and behavioral impairment were most common after prim-6 and prim-16 exposure. By contrast, microphthalmia and growth retardation were stage-independent.<h4>Conclusions</h4>Our findings show that some ethanol effects are strongly stage-dependent. The phenotypes mimic key aspects of FAS including craniofacial abnormality, microphthalmia, growth retardation and behavioral impairment. We also identify a critical time window (prim-6 and prim-16) for ethanol sensitivity. Finally, our identification of a wide phenotypic spectrum is reminiscent of human FAS, and may provide a useful model for studying disease resilience. |
| format | Article |
| id | doaj-art-385f7a28db3a43769102d741d5c26e20 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-385f7a28db3a43769102d741d5c26e202025-08-20T02:13:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e2003710.1371/journal.pone.0020037Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience.Shaukat AliDanielle L ChampagneAlia AliaMichael K Richardson<h4>Background</h4>In humans, ethanol exposure during pregnancy causes a spectrum of developmental defects (fetal alcohol syndrome or FAS). Individuals vary in phenotypic expression. Zebrafish embryos develop FAS-like features after ethanol exposure. In this study, we ask whether stage-specific effects of ethanol can be identified in the zebrafish, and if so, whether they allow the pinpointing of sensitive developmental mechanisms. We have therefore conducted the first large-scale (>1500 embryos) analysis of acute, stage-specific drug effects on zebrafish development, with a large panel of readouts.<h4>Methodology/principal findings</h4>Zebrafish embryos were raised in 96-well plates. Range-finding indicated that 10% ethanol for 1 h was suitable for an acute exposure regime. High-resolution magic-angle spinning proton magnetic resonance spectroscopy showed that this produced a transient pulse of 0.86% concentration of ethanol in the embryo within the chorion. Survivors at 5 days postfertilisation were analysed. Phenotypes ranged from normal (resilient) to severely malformed. Ethanol exposure at early stages caused high mortality (≥88%). At later stages of exposure, mortality declined and malformations developed. Pharyngeal arch hypoplasia and behavioral impairment were most common after prim-6 and prim-16 exposure. By contrast, microphthalmia and growth retardation were stage-independent.<h4>Conclusions</h4>Our findings show that some ethanol effects are strongly stage-dependent. The phenotypes mimic key aspects of FAS including craniofacial abnormality, microphthalmia, growth retardation and behavioral impairment. We also identify a critical time window (prim-6 and prim-16) for ethanol sensitivity. Finally, our identification of a wide phenotypic spectrum is reminiscent of human FAS, and may provide a useful model for studying disease resilience.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0020037&type=printable |
| spellingShingle | Shaukat Ali Danielle L Champagne Alia Alia Michael K Richardson Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience. PLoS ONE |
| title | Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience. |
| title_full | Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience. |
| title_fullStr | Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience. |
| title_full_unstemmed | Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience. |
| title_short | Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience. |
| title_sort | large scale analysis of acute ethanol exposure in zebrafish development a critical time window and resilience |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0020037&type=printable |
| work_keys_str_mv | AT shaukatali largescaleanalysisofacuteethanolexposureinzebrafishdevelopmentacriticaltimewindowandresilience AT daniellelchampagne largescaleanalysisofacuteethanolexposureinzebrafishdevelopmentacriticaltimewindowandresilience AT aliaalia largescaleanalysisofacuteethanolexposureinzebrafishdevelopmentacriticaltimewindowandresilience AT michaelkrichardson largescaleanalysisofacuteethanolexposureinzebrafishdevelopmentacriticaltimewindowandresilience |