Epigenetic impacts of the acaricide flumethrin on honeybees (Apis mellifera)

Epigenetic modifications facilitate organismal adaptation to environmental toxins. While the toxicity of the acaricide flumethrin toward honeybees has been documented, the mechanisms underlying its effects on epigenetic modifications remain unclear. Risk screening revealed a high prevalence of flumethrin residues in honeybee colonies and notable bioaccumulation in honeybee brains following oral exposure. Flumethrin exposure at 10 μg/L (the minimum detected residue level) significantly altered the global levels of multiple epigenetic modifications-including RNA m⁶A, A_m, m⁵C, m⁷G, and DNA 5 mC and 6 mA-along with the expression of related genes. m⁶A-seq demonstrated that flumethrin significantly altered m⁶A methylation on transcripts crucial for neuronal activity and memory within the Hedgehog and Hippo signaling pathways. Critically, m⁶A methylation modulated the transcripts of 12 odorant receptors, correlating with flumethrin-induced olfactory sensitivity deficits confirmed by electroantennography. Additionally, flumethrin altered methylation on transcripts encoding stress sensors and immune modulators in the FoxO and MAPK signaling pathways, triggering defense responses. The induced epigenetic marks and m⁶A-mediated transcripts, including EDD1, PI3K, Ptc, FoxO, Jra, and Argk, can be regarded as potential biomarkers for neurotoxicity assessment in honeybees. Our findings provide novel mechanistic insights into flumethrin toxicity and support a framework for epigenetic biomarkers in assessing environmental risks to honeybees.