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| Status |
Public on Jan 11, 2022 |
| Title |
Sex differences in embryonic gonad transcriptomes and benzo[a]pyrene metabolite levels after transplacental exposure |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are generated during incomplete combustion of organic materials. Prior research has demonstrated that BaP is a prenatal ovarian toxicant and carcinogen. However, the metabolic pathways active in the embryo and its developing gonads and the mechanisms by which prenatal exposure to BaP predisposes to ovarian tumors later in life remain to be fully elucidated. To address these data gaps, we orally dosed pregnant female mice with BaP from E6.5-11.5 (0, 0.2 or 2 mg/kg-day) for metabolite measurement or E9.5-11.5 (0 or 3.33 mg/kg-day) for embryonic gonad RNA-sequencing. Embryos were harvested at E13.5 for both experiments. The sum of BaP metabolite concentrations increased significantly with dose in the embryos and placentas, and concentrations were significantly higher in female than male embryos and in embryos than placentas. RNA sequencing revealed that enzymes involved in metabolic activation of BaP are expressed at moderate to high levels in embryonic gonads and that greater transcriptomic changes occurred in the ovaries in response to BaP than in the testes. We identified 490 differentially expressed genes (DEGs) with FDR p-values <0.05 when comparing BaP-exposed to control ovaries, but no statistically significant DEGs between BaP-exposed and control testes. Genes related to monocyte/macrophage recruitment and activity, prolactin family genes, and several keratin genes were among the most upregulated genes in the BaP-exposed ovaries. Results show that developing ovaries are more sensitive than testes to prenatal BaP exposure, which may be related to higher concentrations of BaP metabolites in female embryos.
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| Overall design |
Pregnant mice were exposed to benzo[a]pyrene, and gonads were collected from E13.5 embryos for RNA-seq.
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| Contributor(s) |
Shioda T, Lim J, Luderer U, Ramesh A, Leon K |
| Citation(s) |
34734245 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 ES020454 |
Developmental Gene-Environment Interactions and Premature Ovarian Failure |
The Regents of the University of California |
Ulrike Luderer |
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| Submission date |
Sep 20, 2021 |
| Last update date |
Apr 13, 2022 |
| Contact name |
Toshi Shioda |
| E-mail(s) |
tshioda@partners.org
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| Phone |
(617) 726-3425
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| Organization name |
MGH Cancer Center
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| Department |
Center for Cancer Research
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| Lab |
Molecular Profiling Lab
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| Street address |
Building 149 - 7th Floor, 13th Street
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| City |
Charlestown |
| State/province |
MA |
| ZIP/Postal code |
02129 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (23)
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| GSM5588511 |
Ovary, BaP, 1-4 |
| GSM5588512 |
Testis, oil, 1-5 |
| GSM5588513 |
Testis, oil, 1-6 |
| GSM5588514 |
Testis, BaP, 1-8 |
| GSM5588515 |
Ovary, oil, 2-1 |
| GSM5588516 |
Ovary, oil, 2-2 |
| GSM5588517 |
Ovary, BaP, 2-3 |
| GSM5588518 |
Ovary, Bap, 2-4 |
| GSM5588519 |
Testis, oil, 2-5 |
| GSM5588520 |
Testis, oil, 2-6 |
| GSM5588521 |
Testis, BaP, 2-7 |
| GSM5588522 |
Testis, BaP, 2-8 |
| GSM5588523 |
Ovary, oil, 3-1 |
| GSM5588524 |
Ovary, oil, 3-2 |
| GSM5588525 |
Ovary, BaP, 3-3 |
| GSM5588526 |
Ovary, BaP, 3-4 |
| GSM5588527 |
Testis, oil, 3-5 |
| GSM5588528 |
Testis, oil, 3-6 |
| GSM5588529 |
Testis, BaP, 3-7 |
| GSM5588530 |
Testis, BaP, 3-8 |
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| Relations |
| BioProject |
PRJNA764582 |
| SRA |
SRP337838 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE184417_RNAseq_filtered_normalized_counts.xlsx |
4.9 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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