Towards an understanding of the developmental zebrafish (Danio rerio) proteome and impacts of age-specific sensitivities with a model toxicant.

Chemicals, waste, and pollution represent a growing international concern in the face of increasingly urbanized ecosystems. At least 350,000 chemicals and mixtures are registered for use internationally, but many lack basic toxicological safety information. Thus, it is necessary for modern toxicology approaches to employ the adverse outcome pathway (AOP) framework and new approach methodologies to increase throughput, reduce cost, and link molecular interactions to organismal and population scale consequences through the use of omic tools and alternative models. Proteomics is of particular interest within this framework as most molecular AOP interactions occur at the protein level and dictate biological structure-function relationships. Here, I first identified diverse procedures, practices, and reporting gaps present in the fish toxicology proteomics literature and recommended opportunities for development of reporting guidelines, increased QA/QC, and method optimization to reduce inconsistencies among future studies. Early life stage zebrafish have gained popularity as an animal alternative with incorporation into standardized methods (such as Organisation for Economic Cooperation and Development test guideline no. 236) to become arguably the most important alternative vertebrate model of the current day. Interestingly, baseline expression dynamics are poorly understood throughout the zebrafish life cycle, especially related to toxicologically relevant biomolecules and animal alternative life stages. Leveraging proteomic tools, I identified differential enrichment of evolutionarily conserved processes, periods of metabolic stress, variable expression of toxicological targets, and developmental immaturity of organ systems in larval zebrafish at previously understudied stages. Lastly, developmental sensitivity to chemicals is poorly studied, particularly for proteome responses across chemical concentrations. I identified age-specific behavior and protein expression dynamics in response to multiple concentrations of a model pharmaceutical. Interestingly, differential protein and pathway enrichment of larval zebrafish were consistent with biological responses reported in human pharmaceutical data. Additionally, differences in expression of key protein targets, biochemical pathways, and developmental maturity of organ systems may contribute to observed age specific sensitivity differences within embryos and later larval stages of an important animal alternative model. Such whole-body protein expression observations to a model pharmaceutical with development provides a foundation to further examine how toxicants and toxins influence age-specific adverse outcomes.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Doctoral

Grantor

Baylor University.

Year dc:date.issued

2026

Author dc:creator

• Henke, Abigail N., 1997-

Advisor dc:contributor.advisor

• Brooks, Bryan W.

• Proteomics.
• Zebrafish.
• Alternative vertebrate.
• Age.
• Pharmaceuticals.

Statement dc:rights

• Baylor University works are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission.

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/2104/14833

OAI identifier oai:identifier

oai:baylor-ir.tdl.org:2104/14833