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Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE182523 | GEO | 2023/07/31

REPOSITORIES: GEO

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Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures I

Project description:We report the results of treatment of embryonic limbs with bisphenols A. RNA sequencing was performed to measure differential expression as a result of exposure compared to DMSO treated control limbs.

2023-07-31 | GSE182039 | GEO

Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures III

Project description:We report the results of treatment of embryonic limbs with bisphenol S. RNA sequencing was performed to measure differential expression as a result of exposure to BPS compared to DMSO treated control limbs.

2023-07-31 | GSE182521 | GEO

Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures II

Project description:We report the results of treatment of embryonic limbs with bisphenol AF. RNA sequencing was performed to measure differential expression as a result of exposure to BPAF compared to DMSO treated control limbs.

2023-07-31 | GSE182046 | GEO

Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures

Project description:Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures

| PRJNA756564 | ENA

Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures III

Project description:Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures III

| PRJNA756566 | ENA

Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures I

Project description:Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures I

| PRJNA754323 | ENA

Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures II

Project description:Effects of BPA, BPAF, and BPS on Endochondral Ossification and on the Transcriptome of Ex Vivo Murine Limb Bud Cultures II

| PRJNA754363 | ENA

Effects of an Environmentally Relevant Mixture of Organophosphate Esters Derived From House Dust on Endochondral Ossification in Murine Limb Bud Cultures.

Project description:Organophosphate esters (OPEs) are used widely as flame retardants and plasticizers but much remains unknown about their potential toxicity. Previously, we reported that 4 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: collagen type II alpha 1-enhanced cyan fluorescent protein (proliferative chondrocytes), collagen type X alpha 1-mCherry (hypertrophic chondrocytes), and collagen type I alpha 1-yellow fluorescent protein (osteoblasts). Limbs were cultured for 6 days in the presence of vehicle or dilutions of the OPE mixture (1/1 000 000, 1/600 000, and 1/300 000). All 3 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-seq 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.

| S-EPMC7916738 | biostudies-literature

Effects of an environmentally relevant mixture of organophosphate esters derived from house dust on endochondral ossification in murine limb bud cultures

Project description: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.

2020-12-28 | GSE157940 | GEO

Exposure to tert-butylphenyl diphenyl phosphate, an organophosphate ester flame retardant and plasticizer, alters hedgehog signaling in ex vivo murine limb bud cultures

Project description:Organophosphate esters (OPEs) have become widely used as flame retardants since the global phase out of polybrominated diphenyl ethers (PBDEs). Previously, we demonstrated that some OPEs, such as tert-butylphenyl diphenyl phosphate (BPDP), were more detrimental to endochondral ossification in ex vivo murine limb bud cultures than one of the major PBDEs that they replaced, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). Here we used a transcriptomic approach to elucidate the mechanism of action of BPDP in the developing limb. Limb buds collected from gestation day 13 CD1 mouse embryos were cultured for 3 or 24 hours in the presence of vehicle, 1 μM, or 10 μM BPDP. RNA sequencing (RNA-seq) analyses revealed that exposure to 1 µM BPDP for 24 hours increased the expression of 5 transcripts, including Ihh, and decreased 14 others, including Gli1, Ptch1, Ptch2, and other targets of Hedgehog (Hh) signaling. Pathway analysis inferred the inhibition of Hh signaling. Attenuation of Hh signaling activity began earlier and reached a greater magnitude after exposure to 10 µM BPDP. Since this pathway is part of the regulatory network governing endochondral ossification, we used a known Hh agonist, purmorphamine, to determine the contribution of Hh signaling inhibition to the negative impact of BPDP on endochondral ossification. Co-treatment of limbs with purmorphamine rescued the detrimental morphological changes in the cartilage template induced by BPDP exposure though it did not restore the expression of key transcription factors, Runx2 and Sp7, to control levels. These data highlight Hh signaling as a developmentally important pathway vulnerable to environmental chemical exposures.

2020-10-01 | GSE155435 | GEO

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