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| Status |
Public on Sep 09, 2022 |
| Title |
Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Growing evidence point towards a strong contribution of paternal factors in placental health with implications in adult-onset complex disease risk. We have recently demonstrated that paternal diet-induced obesity alters sperm histone methylation and is associated with metabolic disturbances in the next generation. Diet-sensitive epigenetic regions in sperm were found at genes involved in trophectoderm and placental development, and corresponded to epigenetic and gene expression profiles in these tissues. We sought to investigate whether paternal diet-induced obesity before conception can alter the placental transcriptome, and whether differential gene expression corresponds with sperm obesity-associated epigenetic signatures. C57BL6/J males were fed either a control or high-fat diet for 10 weeks beginning at 6 weeks of age. They were then bred to control-fed C57BL6/J females to induce pregnancies and E14.5 placentas were collected. RNA-sequencing was performed (n=4 per group per sex) to detect sex-specific transcriptional changes associated with paternal diet. At necropsy, sperm was collected for chromatin immunoprecipitation followed by sequencing (ChIP-seq; n=3 per group) targeting histone H3 lysine 4 tri-methylation (H3K4me3) to detect obesity-induced changes in H3K4me3 enrichment. There were sex-specific differentially expressed genes in placentas with some overlapping with promoters showing obesity-associated sperm epimutations. A deconvolution analysis using single-cell RNA-seq data from mouse E14.5 placenta (Han et al., Cell, 2018) revealed significant differences in trophoblast subtype proportions in placentas derived from HFD sires. This study highlights a previously underappreciated role of the placenta at the origin of paternally-induced metabolic disturbances in offspring.
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| Overall design |
Examination of sperm H3K4me3 in control or high-fat fed sires (n=3 per group), examination of E14.5 placenta total RNA derived from control or high-fat fed sires (n=4 per sex per group)
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| Contributor(s) |
Pepin A, Kimmins S |
| Citation missing |
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| Submission date |
Jun 30, 2022 |
| Last update date |
Sep 11, 2022 |
| Contact name |
Anne-Sophie Pépin |
| E-mail(s) |
anne-sophie.pepin@mail.mcgill.ca
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| Organization name |
McGill University
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| Department |
Department of Pharmacology and Therapeutics
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| Street address |
21111 Lakeshore road
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| City |
Sainte-Anne-de-Bellevue |
| State/province |
QC |
| ZIP/Postal code |
H9X3V9 |
| Country |
Canada |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE207326 |
Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition |
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| Relations |
| BioProject |
PRJNA854827 |
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