Sex blind: bridging the gap between drug exposure and sex-related gene expression in Danio rerio using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies

The sex of both humans and Danio rerio has previously been shown to affect the way individuals respond to drug exposure. Genes which allow identification of sex in juvenile zebrafish show potential to reveal these confounding variables between sex in toxicological and preclinical trials but the link...

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Main Authors: Alex C. King, Armin K. Zenker
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Toxicology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/ftox.2023.1187302/full
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author Alex C. King
Armin K. Zenker
author_facet Alex C. King
Armin K. Zenker
author_sort Alex C. King
collection DOAJ
description The sex of both humans and Danio rerio has previously been shown to affect the way individuals respond to drug exposure. Genes which allow identification of sex in juvenile zebrafish show potential to reveal these confounding variables between sex in toxicological and preclinical trials but the link between these is so far missing. These sex-specific, early expressed genes where expression is not altered by drug exposure must be carefully selected for this purpose. We aimed to discover genes which can be used in pharmaceutical trials and environmental toxicology studies to uncover sex-related variations in gene expression with drug application using the model organism Danio rerio. Previously published early sex determining genes from King et al. were evaluated as well as additional genes selected from our zebrafish Next-generation sequencing (NGS) data which are known from previously published works not to be susceptible to changes in expression with drug exposure. NGS revealed a further ten female-specific genes (vtg1, cyp17a1, cyp19a1a, igf3, ftz-f1, gdf9, foxl2a, Nr0b1, ipo4, lhcgr) and five male related candidate genes (FKBP5, apobb1, hbaa1, dmrt1, spata6) which are also expressed in juvenile zebrafish, 28 days post fertilisation (dpf). Following this, a literature review was performed to classify which of these early-expressed sex specific genes are already known to be affected by drug exposure in order to determine candidate genes to be used in pharmaceutical trials or environmental toxicology testing studies. Discovery of these early sex-determining genes in Danio rerio will allow identification of sex-related responses to drug testing to improve sex-specific healthcare and the medical treatment of human patients.
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spelling doaj.art-878e2eb8d66f4abca064af9e4feae8522023-06-16T05:24:48ZengFrontiers Media S.A.Frontiers in Toxicology2673-30802023-06-01510.3389/ftox.2023.11873021187302Sex blind: bridging the gap between drug exposure and sex-related gene expression in Danio rerio using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studiesAlex C. KingArmin K. ZenkerThe sex of both humans and Danio rerio has previously been shown to affect the way individuals respond to drug exposure. Genes which allow identification of sex in juvenile zebrafish show potential to reveal these confounding variables between sex in toxicological and preclinical trials but the link between these is so far missing. These sex-specific, early expressed genes where expression is not altered by drug exposure must be carefully selected for this purpose. We aimed to discover genes which can be used in pharmaceutical trials and environmental toxicology studies to uncover sex-related variations in gene expression with drug application using the model organism Danio rerio. Previously published early sex determining genes from King et al. were evaluated as well as additional genes selected from our zebrafish Next-generation sequencing (NGS) data which are known from previously published works not to be susceptible to changes in expression with drug exposure. NGS revealed a further ten female-specific genes (vtg1, cyp17a1, cyp19a1a, igf3, ftz-f1, gdf9, foxl2a, Nr0b1, ipo4, lhcgr) and five male related candidate genes (FKBP5, apobb1, hbaa1, dmrt1, spata6) which are also expressed in juvenile zebrafish, 28 days post fertilisation (dpf). Following this, a literature review was performed to classify which of these early-expressed sex specific genes are already known to be affected by drug exposure in order to determine candidate genes to be used in pharmaceutical trials or environmental toxicology testing studies. Discovery of these early sex-determining genes in Danio rerio will allow identification of sex-related responses to drug testing to improve sex-specific healthcare and the medical treatment of human patients.https://www.frontiersin.org/articles/10.3389/ftox.2023.1187302/fullsex-variationgene expressionzebrafishdrug influencehuman health
spellingShingle Alex C. King
Armin K. Zenker
Sex blind: bridging the gap between drug exposure and sex-related gene expression in Danio rerio using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies
Frontiers in Toxicology
sex-variation
gene expression
zebrafish
drug influence
human health
title Sex blind: bridging the gap between drug exposure and sex-related gene expression in Danio rerio using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies
title_full Sex blind: bridging the gap between drug exposure and sex-related gene expression in Danio rerio using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies
title_fullStr Sex blind: bridging the gap between drug exposure and sex-related gene expression in Danio rerio using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies
title_full_unstemmed Sex blind: bridging the gap between drug exposure and sex-related gene expression in Danio rerio using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies
title_short Sex blind: bridging the gap between drug exposure and sex-related gene expression in Danio rerio using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies
title_sort sex blind bridging the gap between drug exposure and sex related gene expression in danio rerio using next generation sequencing ngs data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies
topic sex-variation
gene expression
zebrafish
drug influence
human health
url https://www.frontiersin.org/articles/10.3389/ftox.2023.1187302/full
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