Molybdenum disulfide (MoS2) nanosheets are
increasingly
applied in several fields, but effective and accurate strategies to
fully characterize potential risks to soil ecosystems are lacking.
We introduce a coelomocyte-based in vivo exposure
strategy to identify novel adverse outcome pathways (AOPs) and molecular
endpoints from nontransformed (NTMoS2) and ultraviolet-transformed
(UTMoS2) MoS2 nanosheets (10 and 100 mg Mo/L)
on the earthworm Eisenia fetida using
nontargeted lipidomics integrated with transcriptomics. Machine learning-based
digital pathology analysis coupled with phenotypic monitoring was
further used to establish the correlation between lipid profiling
and whole organism effects. As an ionic control, Na2MoO4 exposure significantly reduced (61.2–79.5%) the cellular
contents of membrane-associated lipids (glycerophospholipids) in earthworm
coelomocytes. Downregulation of the unsaturated fatty acid synthesis
pathway and leakage of lactate dehydrogenase (LDH) verified the Na2MoO4-induced membrane stress. Compared to conventional
molybdate, NTMoS2 inhibited genes related to transmembrane
transport and caused the differential upregulation of phospholipid
content. Unlike NTMoS2, UTMoS2 specifically
upregulated the glyceride metabolism (10.3–179%) and lipid
peroxidation degree (50.4–69.4%). Consequently, lipolytic pathways
were activated to compensate for the potential energy deprivation.
With pathology image quantification, we report that UTMoS2 caused more severe epithelial damage and intestinal steatosis than
NTMoS2, which is attributed to the edge effect and higher
Mo release upon UV irradiation. Our results reveal differential AOPs
involving soil sentinel organisms exposed to different Mo forms, demonstrating
the potential of liposome analysis to identify novel AOPs and furthermore
accurate soil risk assessment strategies for emerging contaminants.