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Embryonic exposure to decitabine induces multiple neural tube defects in developing zebrafish

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Abstract

Neural tube defects are severe congenital disorders of the central nervous system that originate during embryonic development when the neural tube fails to close completely. It affects one to two infants per 1000 births. The aetiology is multifactorial with contributions from both genetic and environmental factors. Dysregulated epigenetic mechanisms, in particular the abnormal genome-wide methylation during embryogenesis, have been linked to developmental abnormalities including neural tube defects. The current study investigated the influence of decitabine (DCT), a DNA methylation inhibitor, on embryonic development in zebrafish, with a focus on neural tube formation. The developing zebrafish embryos were exposed to graded concentrations of decitabine (from 13.69 μM to 1 mM) before the onset of neurulation. The developmental process was monitored at regular time intervals post fertilization. At 120 h post fertilization, the developing embryos were inspected individually to determine the incidence and severity of neural tube defects. Using alizarin red staining, the cranial and caudal neural tube morphology was examined in formaldehyde fixed larvae. Anomalies in neural tube and somite development, as well as a delay in hatching, were discovered at an early stage of development. As development continued, neural tube defects became increasingly evident, and there was a concentration-dependent rise in the prevalence and severity of various neural tube defects. 90% of growing embryos in the group exposed to decitabine 1 mM had multiple neural tube malformations, and 10% had isolated neural tube defects. With several abnormalities, the caudal region of the neural tube was seriously compromised. The histopathological studies supported the malformations in neural tube. Our study revealed the harmful impact of decitabine on the development of the neural tube in growing zebrafish. Moreover, these findings support the hypothesis that the hypomethylation during embryonic development causes neural tube defects.

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Acknowledgements

The authors are thankful to the management “The Erode College of Pharmacy and Research Institute”, Erode, Tamil Nadu, India affiliated to Tamil Nadu Dr. M.G.R. Medical University for providing necessary facilities to carry out the research work.

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  1. Department of Pharmacology, The Erode College of Pharmacy and Research Institute affiliated to The Tamil Nadu Dr. M.G.R. Medical University, Veppampalayam, Vallipurathampalayam (Po), Erode, Chennai, Tamil Nadu, 638112, India

    Venugopalan Rajesh & Pachangattupalayam Karuppusamy Divya

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  1. Venugopalan Rajesh
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The experimental study was designed, performed and analyzed by VR and PKD. VR wrote the manuscript and revised the manuscript. PKD approved the final version of the manuscript.

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Correspondence to Venugopalan Rajesh.

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This study was approved by Institutional Animal Ethics Committee (Proposal No. ECP-IAEC-007-2021-2022) under the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA, New Delhi, India).

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Rajesh, V., Divya, P.K. Embryonic exposure to decitabine induces multiple neural tube defects in developing zebrafish. Fish Physiol Biochem 49, 1357–1379 (2023). https://doi.org/10.1007/s10695-023-01261-x

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