Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero can result in osteogenic defect during palatogenesis, but the effects on other craniofacial bones and underlying mechanisms remain to be characterized. By treating pregnant mice with TCDD (40 μg/kg) at the vital craniofacial patterning...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S014765132500079X |
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| author | Xiao-ming Wang Cai-ming Qin Dou Li Xin-ran Xu Xiao-jing Pan Hui Xue |
| author_facet | Xiao-ming Wang Cai-ming Qin Dou Li Xin-ran Xu Xiao-jing Pan Hui Xue |
| author_sort | Xiao-ming Wang |
| collection | DOAJ |
| description | Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero can result in osteogenic defect during palatogenesis, but the effects on other craniofacial bones and underlying mechanisms remain to be characterized. By treating pregnant mice with TCDD (40 μg/kg) at the vital craniofacial patterning stages (embryonic day 8.5, 10.5 and 12.5), and scanning and reconstructing the skulls at embryonic day 18.5 using microCT, we found that TCDD exposure at the earlier and later patterning stages induced variable craniofacial malformations, including premature fusion of metopic and coronal sutures, truncated palatal processes of maxillary and palatine bones, as well as opening oriented pterygoid processes. Further in vitro determination of the underlying mechanisms using human fetal palatal mesenchymal cells (hFPMCs) revealed that TCDD suppressed a wide variety of osteogenic genes responsible for osteoblast commitment and bone matrix synthesis and mineralization, through activating aryl hydrocarbon receptor (AhR) signaling and subsequently inhibiting estrogen signaling. The attenuation of AhR signaling significantly blocked the osteogenic toxicity, and partly restored the expressing level of estrogen receptor α (ERα). Additional treatment with ERα agonist (PPT) significantly relieved the activation of AhR and rescued the impairment of osteogenesis caused by TCDD. Together, our findings demonstrated that TCDD was teratogenic in numerous cranial neural crest cell-derived craniofacial bone development, and disrupted multiple genes for osteogenic differentiation via the TCDD-mediated AhR/ ERα signaling cross-talk. |
| format | Article |
| id | doaj-art-9df8783caa504390b2d9473097d8d798 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-9df8783caa504390b2d9473097d8d7982025-02-12T05:30:10ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117743Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in miceXiao-ming Wang0Cai-ming Qin1Dou Li2Xin-ran Xu3Xiao-jing Pan4Hui Xue5Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing (NO: 20JR10RA653 - ZDKF20210401), School of Stomatology, Lanzhou University, Lanzhou, Gansu Province 730000, ChinaKey Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing (NO: 20JR10RA653 - ZDKF20210401), School of Stomatology, Lanzhou University, Lanzhou, Gansu Province 730000, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi 'an Jiaotong University, Xi'an, Shaanxi Province 710004, ChinaKey Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing (NO: 20JR10RA653 - ZDKF20210401), School of Stomatology, Lanzhou University, Lanzhou, Gansu Province 730000, ChinaKey Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing (NO: 20JR10RA653 - ZDKF20210401), School of Stomatology, Lanzhou University, Lanzhou, Gansu Province 730000, ChinaKey Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing (NO: 20JR10RA653 - ZDKF20210401), School of Stomatology, Lanzhou University, Lanzhou, Gansu Province 730000, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi 'an Jiaotong University, Xi'an, Shaanxi Province 710004, ChinaDepartment of Stomatology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, No. 242, Guangji Road, Suzhou, Jiangsu Province 215000, China; Corresponding author.Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero can result in osteogenic defect during palatogenesis, but the effects on other craniofacial bones and underlying mechanisms remain to be characterized. By treating pregnant mice with TCDD (40 μg/kg) at the vital craniofacial patterning stages (embryonic day 8.5, 10.5 and 12.5), and scanning and reconstructing the skulls at embryonic day 18.5 using microCT, we found that TCDD exposure at the earlier and later patterning stages induced variable craniofacial malformations, including premature fusion of metopic and coronal sutures, truncated palatal processes of maxillary and palatine bones, as well as opening oriented pterygoid processes. Further in vitro determination of the underlying mechanisms using human fetal palatal mesenchymal cells (hFPMCs) revealed that TCDD suppressed a wide variety of osteogenic genes responsible for osteoblast commitment and bone matrix synthesis and mineralization, through activating aryl hydrocarbon receptor (AhR) signaling and subsequently inhibiting estrogen signaling. The attenuation of AhR signaling significantly blocked the osteogenic toxicity, and partly restored the expressing level of estrogen receptor α (ERα). Additional treatment with ERα agonist (PPT) significantly relieved the activation of AhR and rescued the impairment of osteogenesis caused by TCDD. Together, our findings demonstrated that TCDD was teratogenic in numerous cranial neural crest cell-derived craniofacial bone development, and disrupted multiple genes for osteogenic differentiation via the TCDD-mediated AhR/ ERα signaling cross-talk.http://www.sciencedirect.com/science/article/pii/S014765132500079XTCDDCraniofacial boneOsteogenesisCleft palateAhR/ ERα cross-talk |
| spellingShingle | Xiao-ming Wang Cai-ming Qin Dou Li Xin-ran Xu Xiao-jing Pan Hui Xue Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice Ecotoxicology and Environmental Safety TCDD Craniofacial bone Osteogenesis Cleft palate AhR/ ERα cross-talk |
| title | Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice |
| title_full | Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice |
| title_fullStr | Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice |
| title_full_unstemmed | Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice |
| title_short | Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice |
| title_sort | comprehensive three dimensional microct and signaling analysis reveal the teratogenic effect of 2 3 7 8 tetrachlorodibenzo p dioxin on craniofacial bone development in mice |
| topic | TCDD Craniofacial bone Osteogenesis Cleft palate AhR/ ERα cross-talk |
| url | http://www.sciencedirect.com/science/article/pii/S014765132500079X |
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