Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression

Background: Lithium is a first-line treatment for Bipolar Affective Disorder in pregnant women, but it has a narrow therapeutic range and has been shown to cause teratogenic effects on the foetus. This study aimed to investigate the molecular mechanism of lithium–induced heart and eye malformation d...

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Main Authors: Fakurazi, Sharida, Rahmi, Koyuki Atifa, Rohman, Mohammad Saifur, Khotimah, Husnul, Sujuti, Hidayat
Format: Article
Published: A and V Publication 2024
Online Access:http://psasir.upm.edu.my/id/eprint/117918/
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author Fakurazi, Sharida
Rahmi, Koyuki Atifa
Rohman, Mohammad Saifur
Khotimah, Husnul
Sujuti, Hidayat
author_facet Fakurazi, Sharida
Rahmi, Koyuki Atifa
Rohman, Mohammad Saifur
Khotimah, Husnul
Sujuti, Hidayat
author_sort Fakurazi, Sharida
building UPM Institutional Repository
collection Online Access
description Background: Lithium is a first-line treatment for Bipolar Affective Disorder in pregnant women, but it has a narrow therapeutic range and has been shown to cause teratogenic effects on the foetus. This study aimed to investigate the molecular mechanism of lithium–induced heart and eye malformation during organogenesis. Methods: Zebrafish (Danio rerio) was used as the animal model. Zebrafish embryos were exposed to LiCl with concentrations of 0 (control), 3, 30, and 300 mg/L from 1 hpf to 72 hpf. Expression of heart organogenesis-associated genes nkx2.5, nppa, and myl7, and Eye Field Transcription Factors six3a and rx3 were measured using qPCR. Heart and eye morphology were observed using light microscopy and assessed based on representative score assignment for zebrafish teratogenicity assay. Results: In heart organogenesis, LiCl caused significant upregulation of nkx2.5 expression and increased the incidence and severity of heart malformations and contractility malfunction in zebrafish larvae. In eye organogenesis, LiCl caused substantial downregulation of six3a expression and a significant increase in the incidence and severity of eye malformations in zebrafish larvae. Conclusions: LiCl exposure towards zebrafish during the embryonic period disrupted heart and eye organogenesis by changing the expression of transcription factors involved in the respective organogenesis processes.
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institution Universiti Putra Malaysia
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spelling upm-1179182025-06-17T02:18:08Z http://psasir.upm.edu.my/id/eprint/117918/ Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression Fakurazi, Sharida Rahmi, Koyuki Atifa Rohman, Mohammad Saifur Khotimah, Husnul Sujuti, Hidayat Background: Lithium is a first-line treatment for Bipolar Affective Disorder in pregnant women, but it has a narrow therapeutic range and has been shown to cause teratogenic effects on the foetus. This study aimed to investigate the molecular mechanism of lithium–induced heart and eye malformation during organogenesis. Methods: Zebrafish (Danio rerio) was used as the animal model. Zebrafish embryos were exposed to LiCl with concentrations of 0 (control), 3, 30, and 300 mg/L from 1 hpf to 72 hpf. Expression of heart organogenesis-associated genes nkx2.5, nppa, and myl7, and Eye Field Transcription Factors six3a and rx3 were measured using qPCR. Heart and eye morphology were observed using light microscopy and assessed based on representative score assignment for zebrafish teratogenicity assay. Results: In heart organogenesis, LiCl caused significant upregulation of nkx2.5 expression and increased the incidence and severity of heart malformations and contractility malfunction in zebrafish larvae. In eye organogenesis, LiCl caused substantial downregulation of six3a expression and a significant increase in the incidence and severity of eye malformations in zebrafish larvae. Conclusions: LiCl exposure towards zebrafish during the embryonic period disrupted heart and eye organogenesis by changing the expression of transcription factors involved in the respective organogenesis processes. A and V Publication 2024 Article PeerReviewed Fakurazi, Sharida and Rahmi, Koyuki Atifa and Rohman, Mohammad Saifur and Khotimah, Husnul and Sujuti, Hidayat (2024) Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression. Research Journal of Pharmacy and Technology, 17 (12). pp. 1-13. ISSN 0974-3618; eISSN: 0974-360X https://rjptonline.org/AbstractView.aspx?PID=2024-17-12-12 10.52711/0974-360X.2024.00875
spellingShingle Fakurazi, Sharida
Rahmi, Koyuki Atifa
Rohman, Mohammad Saifur
Khotimah, Husnul
Sujuti, Hidayat
Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression
title Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression
title_full Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression
title_fullStr Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression
title_full_unstemmed Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression
title_short Lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in Transcription factor expression
title_sort lithium exposure during embryonic stage affetcs heart and eye morphology in zebrafish larvae via changes in transcription factor expression
url http://psasir.upm.edu.my/id/eprint/117918/
http://psasir.upm.edu.my/id/eprint/117918/
http://psasir.upm.edu.my/id/eprint/117918/