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Impact of maternal topiramate ingestion on ossification of skull and appendicular bones in rat fetuses - 29/02/24

Doi : 10.1016/j.morpho.2023.100702 
W.A. Nasr El-Din a, b, B.K. Potu a, , R.A. Fadel a, b, A.H. Salem a, b, R.P. Sequeira c, A. Almarabheh d, M.M.O. El-Fark b
a Department of Anatomy, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain 
b Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt 
c Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain 
d Department of Family and Community Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain 

Corresponding author.

Highlights

The impact of prenatal exposure of topiramate on ossification of the skull and appendicular bones is not adequately studied.
Our results showed a significant delay in ossification of the metacarpal, metatarsal and craniofacial bones in topiramate-exposed fetuses at both doses when compared to control. Also, a significant decrease in the length of ossified part of the long bones of the forelimb and hindlimb in topiramate-exposed fetuses at both doses was noted when compared to control.
In conclusion, prenatal administration of topiramate in doses equivalent to human therapeutic doses delayed ossification and development of craniofacial and appendicular bones in rat fetuses and their effects are not dose dependent at doses investigated. The implications of these findings in women who require topiramate therapy in pregnancy merit further evaluation.

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Summary

The skull and appendicular bones are derived from different embryological sources during their development. The impact of prenatal exposure of topiramate on ossification of these bones is not adequately studied. The goal of this study was to assess the ossification patterns of the craniofacial bones and bones of the forelimbs and hindlimbs in 20-day-old rat fetuses after maternal exposure to topiramate at doses equivalent to human therapeutic doses. Three groups of Sprague-Dawley pregnant rats were used: control, topiramate 50mg/kg/day (T50) and topiramate 100mg/kg/day (T100). Topiramate was given by oral gavage from day 6 to day19 of gestation. Ossification was evaluated in the bones of 20 days fetuses after staining with Alizarin red. Results showed a significant reduction in complete ossified centers of the metacarpal, metatarsal and craniofacial bones in topiramate-exposed fetuses at both doses when compared to the control group. Also, a significant decrease in the length of ossified part of the long bones of the forelimbs and hindlimbs in topiramate-exposed fetuses at both doses was noted when compared to the control group. Crown-rump length and fetal weight were significantly decreased in topiramate treated groups compared to the control group. In all examined groups, there was a positive correlation between the crown-rump length and the lengths of humerus and femur. No abnormalities in the ossified bones and no significant changes in their ossification pattern were observed between the treated groups. In conclusion, prenatal administration of topiramate in doses equivalent to human therapeutic doses delayed ossification and development of craniofacial and appendicular bones in rat fetuses and their effects are not dose dependent at doses investigated. The implications of these findings in women who require topiramate therapy in pregnancy merit further evaluation.

Le texte complet de cet article est disponible en PDF.

Keywords : Topiramate, Ossification, Ossification centers, Appendicular, Craniofacial, Rat fetus


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Vol 108 - N° 360

Article 100702- mars 2024 Retour au numéro
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