Inappropriate
application of pesticides not only causes
sub-lethal
effects on ecosystem service providers but also reduces crop yield
and quality. As a xenobiotic signal molecule, pesticides may interact
with signal transduction receptors in crops, resulting in oxidative
damage and even metabolic perturbations. We discovered that three
neonicotinoid insecticides (NIs), namely, imidacloprid, thiamethoxam,
and clothianidin, at 0.06–0.12 kg ai/ha significantly inhibited
the auxin signal pathway in rice leaves, thereby reducing the intracellular
auxin (IAA) content. Molecular simulation further confirmed that NIs
occupied the binding site where auxin transporter-like proteins 1
(LAX11) and 2 (LAX12), in which Thr253 and Asn66 of LAX11, as well
as Thr244 and Asn57 of LAX12, were bound to the nitroguanidine of
NIs via H-bonds. Meanwhile, Asn66 of LAX11 and Asn57 of LAX12 interacted
with nitroguanidine via aromatic H-bonds. Moreover, phenylpropanoid
biosynthesis was significantly disturbed because of the inhibited
auxin signal pathway. Notably, peroxidase-coding genes were downregulated
with a maximum value greater than 10-fold, resulting in decreased
antioxidant metabolites flavone (37.82%) and lignin content (20.15%).
Ultimately, rice biomass was reduced by up to 25.41% due to the decline
in IAA content and antioxidant capacity. This study deeply explored
the molecular mechanism of metabolic perturbations in crops stressed
by pesticides, thus providing a scientific basis for pesticide environmental
risk assessment and agricultural product safety.