Sex-specific responses to ER-stress in eyestalk of Litopenaeus vannamei

In this study, following Thapsigargin-induced ER-stress, we integrated neuroendocrine, transcriptomic, metabolomic, and functional analyses to investigate the sex-specific responses of the eyestalk to ER-stress in L. vannamei. Results showed distinct temporal changes in eyestalk neuroendocrine factors between sexes. Transcriptomics revealed sex-biased gene enrichment: females exhibited downregulated protein synthesis and energy metabolism pathways but upregulated lipid and antioxidant pathways; males showed enhanced ER protein processing and suppressed apoptosis, along with impaired glutathione metabolism. Metabolomics identified more than 200 differential metabolites between females and males. Eyestalk ablation confirmed its essential role in survival under ER-stress, with males exhibiting higher dependence. Functional validations demonstrated that females may rely on an α-linolenic acid-fatty acid oxidation axis (FAO) to alleviate oxidative damage, whereas males likely depend on an ABC transporter-glutathione detoxification pathway. Inhibition of FAO in females worsened stress sensitivity, while glutathione precursor supplementation in males improved survival and redox balance. These findings reveal that female and male L. vannamei employ divergent neuroendocrine-metabolic strategies under ER-stress: females may activate lipid reprogramming and antioxidant responses, whereas males appear to enhance protein folding and GSH-mediated detoxification while inhibiting apoptosis. This work provides mechanistic insights into sex-based stress adaptation in crustaceans and supports sex-specific management in shrimp aquaculture.