The effects of aromatase inhibitors and selective estrogen receptor modulators on eye development in the zebrafish (Danio rerio)

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-hydgoxyandrostenedione 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.