Using in vitro gastrulation models to assess the teratogenicity of antiviral drugs: dolutegravir and remdesivir
Date
2021
Authors
Contributor
Advisor
Department
Instructor
Depositor
Speaker
Researcher
Consultant
Interviewer
Narrator
Transcriber
Annotator
Journal Title
Journal ISSN
Volume Title
Publisher
Volume
Number/Issue
Starting Page
Ending Page
Alternative Title
Abstract
About 1 in every 33 babies born in the U.S. each year has a major structural birth defect, which is one of the leading causes of infant death. Due to the prevalence of and severe risk associated with birth defects, further investigation into their causes is needed. One of the potential causes of birth defects are teratogens, which include infectious agents such as viruses, as well as the medications that may be prescribed for the treatment of infectious agents. If a woman contracts a virus during pregnancy, it can negatively affect both her health as well as that of the fetus, so proper treatment is imperative. However, the medications may also negatively impact the developing embryo. It is this concept that formed the basis for this study, where the teratogenicity of important antiviral medications (one used to treat HIV and another to treat COVID-19) was examined using in vitro gastrulation models. The in vitro gastrulation models consist of aggregates of mouse or human pluripotent stem cells which undergo axial elongation mimicking the process of gastrulation. As gastrulation is an embryological event critical to generating the basic body plan, a disruption to this process may result in birth defects. Therefore, adverse effects on the growth, elongation, and gene expression in the gastrulation model serve as an indication that exposure to the drugs may be teratogenic. The results of this study demonstrated that both dolutegravir, the anti-HIV medication, and remdesivir, the only FDA-approved treatment for COVID-19, caused significant morphological and molecular changes in the gastrulation model when cell aggregates were exposed to therapeutically relevant concentrations of the drugs. These results suggest that dolutegravir and remdesivir may have teratogenic effects due to the impairment of key developmental processes. This supports the need to seek alternative therapeutic options with a lesser risk to fetal development. The findings also provide insight for further investigations to reveal the mechanisms of their teratogenicity.
Description
Keywords
Developmental biology, Toxicology, Dolutegravir, Embryoid bodies, Remdesivir, Teratogen
Citation
Extent
96 pages
Format
Geographic Location
Time Period
Related To
Related To (URI)
Table of Contents
Rights
All UHM dissertations and theses 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 from the copyright owner.
Rights Holder
Local Contexts
Email libraryada-l@lists.hawaii.edu if you need this content in ADA-compliant format.