Embryonic Flubendiamide Exposure Alters Expression of OTX2 and Other Early Regulators in Domestic Chick Leading to Congenital Eye Defects.

Abstract

Flubendiamide, a phthalic acid diamide insecticide, has been implicated in potential teratogenic effects on non-target organisms, especially during embryonic development. This study examines the impact of flubendiamide on eye development in chick embryos, a well-established model for vertebrate development. Exposure to 0.5 µg/µL of flubendiamide significantly impaired early ocular morphogenesis, resulting in severe defects such as underdeveloped optic cups and the absence of lens and corneal structures. Histopathological analysis demonstrated disrupted optic cup differentiation, while in silico docking studies revealed strong interactions between flubendiamide and key oculogenic proteins, including OTX2, PAX6, and SOX2. These interactions were associated with altered expression patterns of these critical regulators, alongside overexpression of SHH and downregulation of BMP4, BMP7, and FGF8, which are essential for optic vesicle formation and lens differentiation. Additionally, increased CASPASE-3 expression indicated enhanced apoptosis, contributing to the observed ocular anomalies. These findings suggest that flubendiamide disrupts key signaling pathways necessary for proper eye development, potentially leading to congenital eye defects. The study highlights the need for a thorough evaluation of the molecular mechanisms driving flubendiamide-induced teratogenicity to ensure safer pesticide use and protect environmental and human health.