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The effects of aromatase inhibitors and selective estrogen receptor modulators on eye development in the zebrafish
Alia Hamad1, Matthew Kluk, Joshua Fox
1Department of Biology, Center for Molecular, Cellular, and Biological Chemistry, Virginia Military Institute, Lexington, Virginia 24450, USA.
Purpose:
It has been shown that the steroid hormone estrogen plays an important role in the development of the central nervous system. The purpose of these studies was to determine the effect of estrogen on zebrafish eye maturation.
Methods:
In these experiments, the estrogen receptor blockers tamoxifen and clomiphene, selective estrogen receptor modulators (SERMs), were used to determine the role of estrogen in the developing eye by morphometric microscopic techniques. Also, in this study the synthesis of estrogen was inhibited with aminoglutethimide or 4-hydroxyandrostenedione treatments, both of which are aromatase inhibitors (AIs).
Results:
After these various treatments, the zebrafish were analyzed for eye maturation and growth rates, which were significantly diminished with both AI and SERM treatments. In a competition assay, where tamoxifen and excess estrogen were added at the same time normal eye development and body growth took place, indicating that estrogen out-competed tamoxifen and that these phenomena were most likely exerted at the level of the estrogen receptor. Specifically, morphometric analysis revealed a significantly diminished thickness in most retinal layers, and, most particularly, in the two plexiform layers where synaptic contacts are established.
Conclusions:
These studies have demonstrated that the presence of estrogen in the early developing embryo is critical for retinal development and overall body growth.
Insights
Estrogen is critical for zebrafish eye development. Inhibiting estrogen or blocking its receptors significantly reduced eye maturation and retinal layer thickness, confirming estrogen's vital role.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Estrogen is a key steroid hormone influencing central nervous system development.
- Its specific role in eye maturation requires further elucidation.
Purpose of the Study:
- To investigate the impact of estrogen on zebrafish eye maturation.
- To understand estrogen's role in retinal development using pharmacological interventions.
Main Methods:
- Utilized selective estrogen receptor modulators (SERMs) like tamoxifen and clomiphene.
- Inhibited estrogen synthesis using aromatase inhibitors (AIs) such as aminoglutethimide and 4-hydroxyandrostenedione.
- Employed morphometric microscopic techniques for quantitative analysis.
Main Results:
- Both AI and SERM treatments significantly impaired zebrafish eye maturation and growth rates.
- A competition assay demonstrated that estrogen could overcome tamoxifen's inhibitory effects, suggesting a receptor-mediated mechanism.
- Morphometric analysis revealed reduced thickness in retinal layers, particularly the plexiform layers crucial for synaptic connections.
Conclusions:
- Estrogen is essential for normal retinal development in zebrafish embryos.
- The presence of estrogen is critical for overall embryonic growth.
- Findings highlight the importance of estrogen signaling in early visual system development.
