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Mus musculus breed:C57BL/6(Cast7)

ABSTRACT: Mouse Model of Preconception Male Alcohol Exposure

PROVIDER: PRJNA421361 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12455688.fastq.gz	Fastqsanger.gz
	SRR12455689.fastq.gz	Fastqsanger.gz
	SRR12455690.fastq.gz	Fastqsanger.gz
	SRR12455691.fastq.gz	Fastqsanger.gz
	SRR12455692.fastq.gz	Fastqsanger.gz

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RNA-sequencing of liver samples derived from offspring sired by males chronically exposed to alcohol prior to conception

Project description:Using an established mouse model of chronic exposure, previous work by our group had linked preconception paternal alcohol use to sex-specific patterns of fetal growth restriction and placental dysfunction. The goal of the present study was to investigate the long-term impact chronic preconception paternal alcohol exposure has on offspring growth and metabolic programming. In the male offspring, we observed increases in both the expression of genes within the pro-fibrotic TGF-ß signaling pathway as well as total levels of cellular hydroxyproline within the liver. Further, we identified suppressed cytokine profiles, which could be linked to the up-regulation of genes in the LiverX/RetinoidX/FarnesoidX Receptor pathways.

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Project description:Using a mouse model, studies by our group reveal that paternal preconception alcohol intake affects offspring fetal-placental growth, with long-lasting consequences on adult metabolism. Here, we tested the hypothesis that chronic preconception male alcohol exposure impacts histone enrichment in sperm and that these changes are associated with altered developmental programming in the placenta. Using chromatin immunoprecipitation, we find alcohol-induced increases in sperm histone H3 lysine 4 trimethylation (H3K4me3) that map to promoters and presumptive enhancer regions enriched in genes driving neurogenesis and craniofacial development. Given the colocalization of H3K4me3 with the chromatin binding factor CTCF across both sperm and embryos, we next examined CTCF localization in the placenta. We find global changes in CTCF binding within placentae derived from the male offspring of alcohol-exposed sires. Furthermore, altered CTCF localization correlates with dysregulated gene expression across multiple gene clusters; however, these transcriptional changes only occur in male offspring. Finally, we identified a correlation between genomic regions exhibiting alcohol-induced increases in sperm H3K4me3 and increased CTCF binding in male placentae. Collectively, our analysis demonstrates that the chromatin landscape of sperm is sensitive to chronic alcohol exposure and that a subset of these affected regions exhibits increased placental CTCF enrichment.

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Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.

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