Timing of exposure impacts how organophosphorus pesticides affect the developing brain in the planarian Dugesia japonica.

Exposure to organophosphorus pesticides (OPs) during pregnancy has been suggested to cause adverse outcomes on neural development of the fetus but the mechanisms underlying developmental neurotoxicity of OPs remain unclear. While OPs share acetylcholinesterase (AChE) as the primary molecular target, different OPs have been shown to induce different effects in laboratory studies. Previously, we found that OPs differentially affect regenerating planarians when applied on the first day of regeneration. To determine if the timing of OP exposure affects adverse outcomes, here, we performed a comparative study of 5 OPs-chlorpyrifos (17.8 μM), diazinon (16.2 μM), dichlorvos (1 μM), profenofos (10 μM), and malathion (56.2 μM)-in the planarian Dugesia japonica. We evaluated how effects on behavior and nervous system morphology changed with OP exposure starting on different days of regeneration/development. We found that some toxic effects were dependent on the developmental stage during exposure. For example, profenofos impaired brain development when exposure started on day 1 of development but caused lethality when exposure started during later stages. Inhibition of the enzymatic activity of AChE on day 12 of exposure was not affected by the different exposure paradigms, suggesting that the differential effects were either due to effects on the non-enzymatic functions of AChE or on other targets during neurodevelopment. This work provides insight into which neurodevelopmental key events are affected by OP exposure, enabling future mechanistic work to identify the targets underlying OP developmental neurotoxicity.