Preliminary metabolomic insights into the biomarkers associated with late-stage maternal mortality in <i>Eriocheir sinensis</i> H. Milne-Edwards, 1853 (Decapoda: Brachyura: Varunidae)

Abstract Late-stage maternal mortality (LMM) in the Chinese mitten crab (Eriocheir sinensis H. Milne-Edwards, 1853) causes substantial aquaculture losses, yet its biological origin and solution remain unclear. Untargeted plasma metabolomics was utilized to compare moribund and active broodstock across two consecutive years (2024, 2025) to identify stable biomarkers. We detected 1,207 metabolites and principal component analysis confirmed distinct metabolic profiles between years, highlighting significant interannual variability likely due to environmental impacts. Despite this, 20 differentially expressed metabolites (DEMs) consistently altered in both years, implicating key pathways like glycerophospholipid, energy, and amino acid metabolism. A six-metabolite panel, including phenylethylmalonamide and dimethylethanolamine, was identified by random forest model with an area under the receiver operating characteristic curve (AUC) of 0.9904 as a potential diagnostic biomarker with preliminary accuracy. Our current study suggests LMM stems from cumulative metabolic stress induced by brooding and environmental challenges. The identified biomarkers offer a foundation for non-lethal health screening, enabling proactive management to reduce losses and enhance aquaculture sustainability. Our study offers initial mechanistic insights and suggests basic actionable solutions to enhance the sustainability, profitability, and resilience of E. sinensis aquaculture, while emphasizing environmental factors with metabolomics applications.