Multi-omics analysis reveals the cerebral sex-specific responses to chronic hypoxia in yellow catfish (Pelteobagrus fulvidraco)

Hypoxia disrupts multiple physiological processes, including metabolism, immunity, and reproduction in teleosts. The brain plays a critical role in adapting to environmental changes, regulating the endocrine system, and controlling reproduction. The present study investigated the sex-specific cerebral responses to chronic hypoxia through an integrated analysis of the transcriptome, proteome, and metabolome of yellow catfish. Common cerebral responses in both females and males included activation of the HIF signaling pathway, angiogenesis, and improved oxygen delivery by red blood cells. Reproductive defects were indicated by the downregulation of gh1, cga, and tshb in both sexes. Thyroid hormone homeostasis was more severely disrupted by hypoxia in females than in males, accompanied by a significant decrease in the level of VTG in the female brain. Damaged brain function was evidenced by the highly enriched pathways of “cytokine-cytokine receptor interaction” and “ECM-receptor interaction,” and the blood-brain barrier (BBB) also appeared to be disrupted in female fish. In the male brain, reproductive-related genes or proteins, including prl, lepr, and AVP, were specifically decreased. Dysfunction in the male brain was also indicated by the enrichment of pathways such as “cytokine-cytokine receptor interaction” and “neuroactive ligand-receptor interaction,” based on differentially expressed genes (DEGs) and proteins (DEPs). Additionally, chronic hypoxia appeared to inhibit cerebral amino acid metabolism in males. In summary, our results offer insight into understanding the sex-specific cerebral responses induced by chronic hypoxia in teleosts.