STUDY OF NEURAL TUBE DEFECTS AND ASSOCIATED PATHOGENESIS IN CHICK EMBROYS ADMINISTRATED WITH CYCLOPHOSPHAMIDE AND SODIUM VALPROATE.

Background: Neural tube defects (NTDs) are among the most common congenital malformations resulting from failure of neural tube closure during early embryogenesis. Teratogenic agents such as cyclophosphamide and sodium valproate have been implicated in disrupting normal neurulation through oxidative stress, apoptosis, altered folate metabolism, and epigenetic modifications. The chick embryo serves as an established experimental model for investigating the mechanisms underlying neural tube defects because of its accessibility and similarity to vertebrate embryonic development. Objectives: The present study aimed to evaluate the teratogenic effects of cyclophosphamide and sodium valproate on neural tube development in chick embryos and to investigate the associated morphological and histopathological changes involved in the pathogenesis of neural tube defects. Materials and Methods: Fertilized White Leghorn chicken eggs were randomly allocated into control, cyclophosphamide-treated, and sodium valproate-treated groups. The respective drugs were administered during the critical period of neurulation. Embryos were harvested at 24, 48, 72, and 96 hours of incubation and examined for gross morphological abnormalities, developmental delay, neural tube defects, embryonic growth, and mortality. Histopathological examination of neural tissues was performed using hematoxylin and eosin staining. Statistical analysis was carried out using appropriate parametric and non-parametric tests, with p < 0.05 considered statistically significant. Results: Embryos exposed to cyclophosphamide and sodium valproate exhibited significant developmental abnormalities compared with controls. Gross examination demonstrated growth retardation, delayed neurulation, abnormal body curvature, reduced vascularization, and increased embryonic mortality. Sodium valproate produced a higher incidence of open neural tube defects and defective neural fold fusion, whereas cyclophosphamide caused more pronounced embryotoxicity and generalized developmental delay. Histopathological examination revealed neuroepithelial disorganization, reduced neuronal density, cellular degeneration, vacuolation, and incomplete neural tube closure in treated embryos. The severity of abnormalities increased with advancing incubation period and drug exposure. Conclusion: Cyclophosphamide and sodium valproate significantly interfere with normal neurulation in chick embryos by disrupting neuroepithelial proliferation, neural tube closure, and embryonic development. Sodium valproate predominantly induced neural tube defects, while cyclophosphamide produced greater embryotoxic effects. These findings support the usefulness of the chick embryo as an experimental model for studying the pathogenesis of neural tube defects and provide further evidence for the teratogenic potential of these agents.