"Investigation of Chondrogenesis, Myogenesis, and Osteogenesis After 2," by Haley Brashears

Date of Award

12-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Environmental Toxicology

Committee Chair/Advisor

Bain, Lisa

Committee Member

Van de Hurk, Peter

Committee Member

Liu, Qing

Committee Member

Dasgupta, Subham

Abstract

Synthetic phenolic antioxidants (SPAs) are used in personal care products, food packaging, and water pipes, common SPAs include 2,4-di-tert-butylphenol (2,4-DTBP), 2-tert-butyl phenol (2-BP), and 4-tert-butyl phenol (4-BP). These compounds are detected in the environment and in human biological samples. 2,4-DTBP has been detected in cord plasma, placenta, and breast milk samples. This drives the concern regarding developmental toxicity. In human iPS cells 2,4-DTBP impairs differentiation into somites and osteoblasts. Other SPAs, like 2,6-di-tert-butyl-hydroxytoluene caused increased rates of malformations including yolk and pericardial edema, and spinal curvature in 5-day post fertilization (dpf) zebrafish. SPAs can disrupt levels of reactive oxygen species (ROS) which are crucial for differentiation of osteoblasts and chondrocytes. This study aimed to investigate if 2,4-DTBP, 3,5-DTBC, 2-BP, and 4-BP effects development of bone, cartilage, and muscle in zebrafish. Zebrafish were exposed to 2,4-DTBP, 3,5-DTBC, 2-BP, or 4-BP from 1 hour post fertilization to 5 dpf, mortality, hatching, and morphology were assessed. Gene expression was measured and cartilage and bone development was assessed with Alcian blue and Alizarin red staining. 2-BP and 3,5-DTBC significantly decreased expression of sparc, a gene required for bone formation. 3,5-DTBC and 4-BP significantly increased expression sox9a, a transcript required for cartilage formation and myod1, a gene involved in muscle development. Staining analysis revealed 2,4-DTBP and 2-BP significantly reduced length of cartilage structures and the distance between structures. 3,5-DTBC and 4-BP increased both distance and angle of cartilage structures. This study shows that 2,4-DTBP, 3,5-DTBC, 2-BP, and 4-BP differentially alter early development of zebrafish larvae.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.