Developmental toxicity and transcriptome analysis of equine estrogens in developing medaka (Oryzias latipes) using nanosecond pulsed electric field incorporation.
Abstract: Equine estrogens (EQs) are steroidal hormones isolated from the urine of pregnant mares and are used in the formulation of human medications. This study initially investigated the embryonic developmental toxicity of equilin (Eq) and equilenin (Eqn) in medaka (Oryzias latipes). Malformations were observed in embryos exposed to nominal concentrations of 1 and 10 mg/L of Eq and Eqn. Delayed hatching was observed at 1 mg/L of Eq. To further investigate the molecular mechanism of developmental toxicity caused by Eq and Eqn, transcriptome and bioinformatics analyses were performed. Among 2016 and 3855 total differentially expressed genes (DEGs), 1117 DEGs overlapped between Eq. (55.4 % of total DEGs) and Eq. (29.0 % of total DEGs). Gene ontology indicated effects in terms related to blood circulation and cell junctions. Pathway analyses using DEGs revealed that both Eq and Eqn treatments at 10 mg/L affected various KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, such as neuroactive ligand-receptor interaction, mitogen-activated protein kinase signaling, retinol metabolism, and cytokine-cytokine receptor interaction. These results suggest that the disruption of these KEGG pathways is involved in the developmental toxicity of EQs in medaka embryos.
Copyright © 2023. Published by Elsevier Inc.
Publication Date: 2023-01-06 PubMed ID: 36621632DOI: 10.1016/j.cbpc.2023.109547Google Scholar: Lookup
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- Journal Article
Summary
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The research article is about the evaluation of the toxic effects of equine estrogens, hormones derived from the urine of pregnant mares, on the development of medaka fish embryos by analyzing its alterations of gene expressions.
Objective of the Research
- The primary objective of the research was to observe and analyze the possible developmental toxicity from exposure of medaka fish embryos to two types of equine estrogens known as equilin (Eq) and equilenin (Eqn). Medaka embryos were selected for the study due to their transparent eggs, which allows close examination of developmental processes.
Methodology and Results
- The researchers subjected the embryos to varying concentrations of Eq and Eqn. At certain concentrations, physical malformations were observed, including delayed hatching.
- To understand the molecular mechanisms behind these developments, a thorough transcriptome and bioinformatics analyses were undertaken.
Transcriptome and Bioinformatics Analyses
- A large number of genes were found to be differentially expressed in Eq and Eqn treated samples. Among these, a significant overlap was detected, which suggests common pathways that are affected by both Eq and Eqn.
- The Differential Expressed Genes (DEGs) were related to certain gene ontologies, including those linked to blood circulation and cell junctions, which could attribute to the physical abnormalities observed.
- Performing a pathway analysis using the DEGs revealed that treatments at certain concentrations affected several pathways enlisted in the Kyoto Encyclopedia of Genes and Genomes (KEGG). These include pathways related to neuroactive ligand-receptor interaction, mitogen-activated protein kinase signaling, retinol metabolism, and cytokine-cytokine receptor interaction.
Conclusion
- The study concluded that the developmental toxicity in the medaka embryos observed from exposure to equine estrogens is likely due to disruptions in these identified KEGG pathways.
Implications of the Study
- The research findings are important as equine estrogens are used in human medications, which could potentially have an impact on human health. Additionally, the study contributes to understanding the effect of these substances on aquatic organisms and their larger ecosystems.
Cite This Article
APA
Uchida M, Addai-Arhin S, Ishibashi H, Hirano M, Fukushima S, Ishibashi Y, Tominaga N, Arizono K.
(2023).
Developmental toxicity and transcriptome analysis of equine estrogens in developing medaka (Oryzias latipes) using nanosecond pulsed electric field incorporation.
Comp Biochem Physiol C Toxicol Pharmacol, 266, 109547.
https://doi.org/10.1016/j.cbpc.2023.109547 Publication
Researcher Affiliations
- Department of Creative Engineering, National Institute of Technology, Ariake College, 150 Higashi-Hagio, Omuta, Fukuoka 836-8585, Japan.
- Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-100 Higashi-ku, Tsukide, Kumamoto 862-8502, Japan; Pharmaceutical Science Department, Faculty of Health Sciences, Kumasi Technical University, Post Office Box 854, Kumasi, Ghana.
- Graduate School of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
- Department of Bioscience, School of Agriculture, Tokai University, 9-1-1 Toroku, Higashi-ku, Kumamoto, Kumamoto 862-8652, Japan.
- Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-100 Higashi-ku, Tsukide, Kumamoto 862-8502, Japan; Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Univ. St. 1-1-1, Sanyo-Onoda, Yamaguchi 756-0884, Japan.
- Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-100 Higashi-ku, Tsukide, Kumamoto 862-8502, Japan.
- Department of Creative Engineering, National Institute of Technology, Ariake College, 150 Higashi-Hagio, Omuta, Fukuoka 836-8585, Japan. Electronic address: tominaga@ariake-nct.ac.jp.
- Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-100 Higashi-ku, Tsukide, Kumamoto 862-8502, Japan; Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe, Chuo-ku, Kumamoto, Kumamoto 862-0973, Japan.
MeSH Terms
- Animals
- Horses
- Female
- Humans
- Estrogens / toxicity
- Oryzias / genetics
- Oryzias / metabolism
- Gene Expression Profiling
- Equilin / metabolism
- Transcriptome
Conflict of Interest Statement
Declaration of Competing Interest The authors declare that they have no potential conflicts of interest.
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