The acclimation response of fish gills to chronic intermittent hypoxia (CIH) is an important aspect to understand, as anthropogenically induced hypoxia in water bodies has been a stressor for fish for many years and is expected to persist in the future. In order to investigate the acclimation response of fish gills to CIH stress, we conducted a study using largemouth bass (Micropterus salmoides) exposed to intermittent hypoxia (dissolved oxygen level, 2.0mg·L-1) for either 1 or 3h per day, over a period of 8weeks. Our findings indicate that exposure to CIH induced remodeling of the gills and an increase in gill surface area. This remodeling of the gills may be attributed to changes in cell growth and proliferation, which are influenced by the activation of the MAPK signaling pathway. We also observed significant upregulation of genes related to glycolysis (fba, pgam1, pepck, atp-pfk, pfk-2, g6pi, gapd-1, and pk), while genes associated with cholesterol synthesis (3β-hsd, cyp51, dsdr- × 1, dsdr, and dhcr7) were downregulated following CIH exposure. Furthermore, we observed the presence of elongated megamitochondria in mitochondria-rich cells within the gills of fish exposed to hypoxia. Additionally, numerous genes involved in calcium signaling pathways were upregulated in the gills of largemouth bass, suggesting an enhanced sensitivity of gills to environmental cues in hypoxia conditions. However, the expression levels of certain genes related to innate and adaptive immune responses were inhibited following CIH exposure. Moreover, the number of mucous cells decreased after CIH exposure. This may have made the gills more susceptible to infection by pathogens, although it facilitated oxygen uptake. These findings highlight the potential vulnerability of gills to pathogenic organisms in the presence of CIH. Overall, our study contributes to a better understanding of how fish acclimate to CIH.
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