Fetal Sex Does Not Influence Rates of Gastrulation-Stage Alcohol-Induced Craniofacial Malformations in C57BL/6J Mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA998893 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25431600_1.fastq.gz | Fastqsanger.gz | |||
| SRR25431600_2.fastq.gz | Fastqsanger.gz | |||
| SRR25431601_1.fastq.gz | Fastqsanger.gz | |||
| SRR25431601_2.fastq.gz | Fastqsanger.gz | |||
| SRR25431602_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Prenatal alcohol exposure during mouse gastrulation (embryonic day [E] 7 in mice, corresponding to ~3rd week of human pregnancy) impairs eye, facial, and cortical development, recapitulating birth defects characteristic of Fetal Alcohol Syndrome (FAS). However, the impact of sex on the prevalence or severity of craniofacial features associated with FAS is currently unknown. The current study administered either alcohol (2.9g/kg, two i.p. doses, four hours apart) or vehicle control to pregnant C57BL/6J females on E7 and assessed fetal morphology at E17. Whereas sex did not affect fetal size in vehicle-treated litters, alcohol-exposed females were smaller than both control females and alcohol-treated males. Alcohol exposure increased the incidence of eye defects to a similar degree in males and females. Together, this suggests that females might be more sensitive to the general developmental effects of alcohol, but not to the effects of alcohol specifically on the craniofacies. We also established a developmental transcriptional baseline via whole transcriptomic analysis of untreated E7 embryos, and found 214 differentially expressed genes in females vs. males, including those in pathways related to cilia and mitochondria structure and function, histone demethylase activity, and pluripotency.
2024-03-19 | GSE239355 | GEO
Project description:Craniofacial and CNS malformations characteristic of Fetal Alcohol Syndrome are caused by alcohol exposure during gastrulation (embryonic day [E]7 in mice; 2nd – 3rd week of human pregnancy). Genetics are a known contributor to differences in alcohol sensitivity in humans, and between different animal model strains such as C57BL/6J and C57BL/6NHsd mice. To investigate how these two genetically similar mouse strains differ in alcohol sensitivity, we profiled gene expression at baseline (E7.0) and 6 or 12 hours after alcohol exposure (E7.25–E7.5) in gastrulation-stage embryos. Many of the baseline transcriptional differences across strains were associated with immune signaling, indicative of their molecular divergence. Alcohol exposure was associated with a more pronounced transcriptional effect in 6J than in 6N, matching the 6J’s increased sensitivity. Alcohol exposure upregulated pathways related to cell death, stress, and hypoxia, and downregulated proliferation and morphogenic pathways. Dysregulated genes were also associated with craniofacial and CNS defects, but only in the 6J embryos. These data demonstrate the genetic variation that can contribute to the effects of prenatal alcohol and identify impacted molecular pathways, including higher baseline expression of inflammatory signaling genes in 6J embryos that likely increases sensitivity to teratogens such as alcohol. Collectively, our data provide a valuable resource that not only enables the discovery of biomarkers pertinent to prenatal alcohol exposure, but also facilitates the transcriptional comparison of two genetically similar mouse strains at three finely resolved developmental timepoints. To this end, we developed a web-based interactive tool to aid in data exploration available at http://parnell-lab.med.unc.edu/Embryo-Transcriptomics/.
2021-06-01 | GSE163796 | GEO
Project description:Pathogenic variants in SF3B4 are responsible for the acrofacial disorders Nager and Rodriguez Syndrome, also known as SF3B4-related Syndromes, associated with malformations in the head, face, limbs, vertebrae as well as the heart. To uncover the etiology of craniofacial malformations found in SF3B4-related syndromes, mutant mouse lines with homozygous deletion of Sf3b4 in neural crest cells (NCC) were generated. Like in human patients, these embryos had craniofacial and cardiac malformations with variable expressivity and penetrance. The severity and survival of Sf3b4 NCC mutants was modified by the level of Sf3b4 in neighbouring non NCC. RNA sequencing analysis of heads of embryos prior to morphological abnormalities showed significant changes in expression of genes forming the NCC regulatory network, as well an increase in exon skipping. We identified several key transcription factors and histone modifiers involved in craniofacial and cardiac development with increased exon skipping. Increased exon skipping was also associated with use of a more proximal branch point, as well as an enrichment in thymidine bases in the 50bp around the branch points. We propose that decrease in Sf3b4 causes changes in the expression and splicing of transcripts required for proper craniofacial and cardiac development, leading to abnormalities.
2024-11-20 | GSE260990 | GEO
Project description:Prevailing dogma maintains that Fetal Alcohol Syndrome (FAS) craniofacial and neurological birth defects are the sole consequence of maternal alcohol use during pregnancy. Using a physiologically relevant mouse model, we contrasted the incidence of alcohol-related growth and craniofacial defects between offspring derived from maternal, paternal, and dual parental alcohol exposures. Geometric morphometric analyses reveal that maternal, paternal, and dual parental exposures each induce unique craniofacial malformations and program dose-dependent increases in microcephaly, particularly in male offspring. Notably, dual parental exposures do not exhibit additive or synergistic effects; instead, our transcriptomic analyses demonstrate that each treatment programs distinct sex-specific changes in gene expression within the developing brain. Our data are the first to demonstrate that male drinking is a plausible driver of alcohol- related birth defects and that epidemiological examination of male alcohol consumption may help explain the enormous variation in FAS clinical presentations and severity.
2024-06-30 | GSE218362 | GEO
Project description:Gene expression was measured using microarrays in 8 hour postfertilization embryos, comparing control versus ethanol-treated (2 to 8 hours postfertilization) embryos. This experiment was performed to determine the gene expression changes that occur in response to ethanol treatment as a model of fetal alcohol spectrum disorder. Fetal alcohol spectrum disorder (FASD) occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell), prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented to characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression and distribution, which control epiboly and gastrulation, were not affected. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a), which controls epiboly, was significantly reduced in ethanol-exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol-treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue) microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression. Control vs. ethanol-treated zebrafish embryos that were treated from 2 to 8 hours postfertilization. Total RNA from control and ethanol-treated embryos were harvested at 8 hours postfertilization.
2014-07-09 | E-GEOD-48380 | biostudies-arrayexpress
Project description:Congenital malformations in facial bones significantly impact the overall representation of face. Establishing a correlation between gene expression and morphogenesis of craniofacial structures may lead to new discoveries of molecular mechanisms of craniofacial development. Thus in the present investigation we will generate gene expression profiles of different facial bones at different time intervals over a period of 5 years to establish their roles in regulating craniofacial development. To perform global gene expression profiling analysis of mandible and maxilla development and integrate these datasets with cell lineage and quantitative 3D dynamic imaging analyses. In collaboration with the ontology group within the FaceBase consortium, we will define anatomical landmarks and morphometric parameters of the developing mandible and maxilla.
2016-03-24 | E-GEOD-67985 | biostudies-arrayexpress
Project description:Congenital malformations in facial bones significantly impact the overall representation of face. Establishing a correlations between gene expression and morphogenesis of craniofacial structures may lead to new discoveries of molecular mechanisms of craniofacial development. Thus in the present investiation we will generate gene expression profile of different facial bones at different time intrevals over a period of 5 years to establish their roles in regulating craniofacial development
2016-03-24 | GSE67985 | GEO
Project description:Congenital malformations in facial bones significantly impact the overall representation of the face. Establishing correlations between gene expression and morphogenesis of craniofacial structures may lead to new discoveries of molecular mechanisms of craniofacial development. Thus in the present investigation, we will generate gene expression profiles of facial bones at embryo stage 14.5 to establish their roles in regulating craniofacial development.
2017-01-13 | GSE92420 | GEO
Project description:Congenital malformations in facial bones significantly impact the overall representation of the face. Establishing correlations between gene expression and morphogenesis of craniofacial structures may lead to new discoveries of molecular mechanisms of craniofacial development. Thus in the present investigation, we will generate gene expression profiles of facial bones at embryo stage 14.5 to establish their roles in regulating craniofacial development.
2017-01-13 | GSE89904 | GEO
Project description:Gene expression was measured using microarrays in 8 hour postfertilization embryos, comparing control versus ethanol-treated (2 to 8 hours postfertilization) embryos. This experiment was performed to determine the gene expression changes that occur in response to ethanol treatment as a model of fetal alcohol spectrum disorder. Fetal alcohol spectrum disorder (FASD) occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell), prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented to characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression and distribution, which control epiboly and gastrulation, were not affected. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a), which controls epiboly, was significantly reduced in ethanol-exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol-treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue) microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.
2014-07-09 | GSE48380 | GEO