Short- and Long-Term Effects of Chlorpyrifos on Thyroid Hormone Axis and Brain Development in Xenopus laevis.

Introduction: The extensive use of the insecticide chlorpyrifos (CPF) throughout the world has brought increased scrutiny on its environmental and health impact. CPF is a cholinergic neurotoxicant; however, exposure to low noncholinergic doses is associated with numerous neurodevelopmental effects in animal models. In this study, we aimed to assess CPF for its potential to disrupt thyroid hormone signalling and investigate the short- and long-term effects on neurodevelopment by using Xenopus laevis.

Methods: The thyroid hormone (TH) disrupting potential of CPF was assessed using TH-sensitive transgenic Tg(thibz:eGFP) tadpoles. The consequences of early embryonic exposure were examined by exposing fertilized eggs for 72 h to environmentally relevant CPF concentrations (10-10 M and 10-8 M). Three endpoints were evaluated: (1) gene expression in whole embryonic brains immediately after exposure, (2) mobility and brain morphology 1 week after exposure, and (3) brain morphology and axon diameters at the end of metamorphosis (2 months after the exposure).

Results: CPF disrupted TH signalling in Tg(thibz:eGFP) tadpoles. The expression of genes klf9, cntn4, oatp1c1, and tubb2b was downregulated in response to CPF. Tadpoles exposed to CPF exhibited increased mobility and altered brain morphology compared to control tadpoles. Early embryonic exposure of CPF affected myelinated axon diameter, with exposed animals exhibiting shifted frequency distributions of myelinated axons diameters towards smaller diameters in the hindbrain of froglets.

Discussion/conclusion: This study provides more evidence of the endocrine and neurodevelopment disrupting activity of CPF. Further experimental and epidemiological studies are warranted to determine the long-term consequences of early CPF exposure on brain development.