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| Status |
Public on Dec 28, 2020 |
| Title |
Effects of an environmentally relevant mixture of organophosphate esters derived from house dust on endochondral ossification in murine limb bud cultures |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Organophosphate esters (OPEs) are used widely as flame retardants and plasticizers but much remains unknown about their potential toxicity. Previously, we reported that four individual OPEs suppress endochondral ossification in murine limb bud cultures. However, real-life exposure is to complex OPE mixtures. In the present study, we tested the hypothesis that a Canadian household dust-based OPE mixture will affect endochondral ossification in gestation day 13 CD1 mouse embryo limb buds expressing fluorescent markers for the major cell populations involved in the process: COL2A1-ECFP (proliferative chondrocytes), COL10A1-mCherry (hypertrophic chondrocytes), and COL1A1-YFP (osteoblasts). Limbs were cultured for six days in the presence of vehicle or dilutions of the OPE mixture (1/1,000,000, 1/600,000, and 1/300,000). All three OPE mixture dilutions affected cartilage template development and the progression of endochondral ossification, as indicated by the fluorescent markers. The expression of Sox9, the master regulator of chondrogenesis, was unchanged, but the expression of Runx2 and Sp7, which drive chondrocyte hypertrophy and osteoblastogenesis, was dilution-dependently suppressed. RNA sequencing revealed that exposure to the 1/300,000 dilution of the OPE mixture for 24 h downregulated 153 transcripts and upregulated 48 others by at least 1.5-fold. Downregulated transcripts were enriched for those related to the immune system and bone formation. In contrast, upregulated transcripts were enriched for those with stress response functions known to be regulated by ATF4 activation. Thus, exposure to the mixture of OPEs commonly found in house dust may have adverse effects on bone formation.
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| Overall design |
Forelimb buds collected from gestation day 13 CD1 mouse embryos were cultured for 24 hours in the presence of vehicle (DMSO) or 1 in 300,000 dilution of our Canadian house dust based OPE mixture; n = 4.
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| Web link |
https://doi.org/10.1093/toxsci/kfaa180
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| Contributor(s) |
Han Y, Hales BF |
| Citation(s) |
33367866 |
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| Submission date |
Sep 15, 2020 |
| Last update date |
Dec 29, 2020 |
| Contact name |
Barbara F. Hales |
| E-mail(s) |
barbara.hales@mcgill.ca
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| Phone |
514-398-3610
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| Organization name |
McGill University
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| Department |
Pharmacology and Therapeutics
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| Street address |
3655 Prom. Sir William Osler, room 110
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| City |
Montreal |
| State/province |
QC |
| ZIP/Postal code |
H3G 1Y6 |
| Country |
Canada |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| GSM4781505 |
Control 24h rep4 [MC_24_4] |
| GSM4781506 |
1 in 300,000 OPE mixture 24h rep1 [M3_24_1] |
| GSM4781507 |
1 in 300,000 OPE mixture 24h rep2 [M3_24_2] |
| GSM4781508 |
1 in 300,000 OPE mixture 24h rep3 [M3_24_3] |
| GSM4781509 |
1 in 300,000 OPE mixture 24h rep4 [M3_24_4] |
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| Relations |
| BioProject |
PRJNA663449 |
| SRA |
SRP282421 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE157940_M3_24vsMC_24.txt.gz |
3.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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