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Published on: November 17, 2016
Exposure to Excess Phenobarbital Negatively Influences the Osteogenesis of Chick Embryos
Yu Yan1, Xin Cheng1, Ren-Hao Yang1
1Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
Insights
Phenobarbital, an epilepsy drug, can harm embryonic bone development by inhibiting cartilage growth, cell proliferation, and blood vessel formation. This leads to shorter long bones in developing embryos.
Area of Science:
- Developmental Biology
- Pharmacology
- Skeletal Biology
Background:
- Phenobarbital is a common antiepileptic medication.
- Long-term use during pregnancy may cause skeletal defects in embryos.
Purpose of the Study:
- Investigate how phenobarbital causes developmental defects in embryonic long bones.
- Elucidate the underlying mechanisms of phenobarbital-induced skeletal abnormalities.
Main Methods:
- Utilized chick embryos and in vitro models to study long bone development.
- Assessed chondrogenesis, chondrocyte proliferation, and mineralization.
- Examined vascularization, including vascular endothelial growth factor (VEGF) expression and angiogenesis.
- Evaluated endothelial cell function (tube formation, migration).
Main Results:
- Phenobarbital decreased chondrogenesis and chondrocyte proliferation.
- Mineralization was suppressed in both in vivo and in vitro models.
- Delayed vascular invasion and down-regulated VEGF in the hypertrophic zone.
- Inhibited angiogenesis and endothelial cell functions.
Conclusions:
- Phenobarbital exposure results in shortened embryonic long bones.
- Mechanisms include inhibition of mesenchyme differentiation and chondrocyte proliferation.
- Delayed mineralization and impaired vascular invasion contribute to skeletal defects.
Abstract:
Phenobarbital is an antiepileptic drug that is widely used to treat epilepsy in a clinical setting. However, a long term of phenobarbital administration in pregnant women may produce side effects on embryonic skeletogenesis. In this study, we aim to investigate the mechanism by which phenobarbital treatment induces developmental defects in long bones. We first determined that phenobarbital treatment decreased chondrogenesis and inhibited the proliferation of chondrocytes in chick embryos. Phenobarbital treatment also suppressed mineralization in both in vivo and in vitro long bone models. Next, we established that phenobarbital treatment delayed blood vessel invasion in a cartilage template, and this finding was supported by the down-regulation of vascular endothelial growth factor in the hypertrophic zone following phenobarbital treatment. Phenobarbital treatment inhibited tube formation and the migration of human umbilical vein endothelial cells. In addition, it impaired angiogenesis in chick yolk sac membrane model and chorioallantoic membrane model. In summary, phenobarbital exposure led to shortened lengths of long bones during embryogenesis, which might result from inhibiting mesenchyme differentiation, chondrocyte proliferation, and delaying mineralization by impairing vascular invasion.
