Congenital asplenia impairs heme-iron recycling during erythropoiesis in zebrafish.

The spleen is postulated to be a hematopoietic tissue in adult fish; however, clear evidence is still lacking to define its role in hematopoietic activity. In our previous study, a congenitally asplenic zebrafish was generated though gene editing, which provided a new perspective for studying the role of fish spleen in hematopoiesis. In this study, HSC-regulated and erythrocyte marker genes, such as gata1a, gata2, klf1, hbaa1, hbaa2, hbba1 and hbba2 were significantly reduced in congenitally asplenic zebrafish when compared with wild-type (WT). Subsequently, we conducted the transcriptome profiles of whole kidneys from WT and congenitally asplenic zebrafish to explore the possible molecular mechanisms underlying the impaired erythropoiesis caused by congenital asplenia. Our results demonstrated that congenital asplenia might impair heme-iron recycling during erythropoiesis, as evidenced by significant down-regulation of genes associated with iron acquisition (tfr1a, tfa, steap3 and slc25a37) and heme biosynthesis and transport (alas2, fech, uros, urod, copx, ppox and abcb10) in congenitally asplenic zebrafish. In addition, the down-regulation of hemopoiesis-related GO terms, including heme binding, tetrapyrrole binding, iron ion binding, heme metabolic process, heme biosynthetic process, erythrocyte differentiation, iron ion homeostasis and hemoglobin metabolic process confirmed the impaired erythropoiesis induced by congenital asplenia. Our study provides an in-depth understanding of spleen function in regulating heme-iron homeostasis during hematopoiesis, thereby providing valuable insights into pathological responses in splenectomized or congenitally asplenic patients.

Environmentally relevant concentrations of mercury inhibit the growth of juvenile silver carp (Hypophthalmichthys molitrix): Oxidative stress and GH/IGF axis.

Mercury (Hg) is a global environmental contaminant, and excessive mercury levels in water can adversely affect the growth of fish. Silver carp (Hypophthalmichthys molitrix) is one of the important freshwater aquaculture fish in China, and its natural resources have been critically declining. However, the effects of Hg2+ exposure on the growth hormone/insulin-like growth factor (GH/IGF) axis and its toxic mechanism are still unclear. In this study, we systematically evaluated the bioaccumulation, histomorphology, antioxidant status, hormone levels, and GH/IGF axis toxicity of juvenile silver carp after exposure to environmental-related concentrations of Hg2+ (0, 0.05, 0.5, 5, and 50 µg/L) for 28 days. Results showed that the Hg2+ bioaccumulation in the liver increased with a rise in Hg2+ concentration and time of exposure. The body length (BL), body weight (BW), weight growth rate (WGR) and specific growth rate (SGR) all decreased after Hg2+ exposure. The serum levels of growth hormones (GH and IGF) and thyroid hormones (T3 and T4) were significantly decreased, and the expressions of GH/IGF axis-related genes were significantly downregulated after 7, 14, and 28 days of Hg2+ exposure. Correlations between the growth parameters and growth hormones or expression of genes in GH/IGF axis further suggested that environmentally relevant concentrations of Hg2+ could have adverse effects on growth. In addition, with increasing Hg2+ exposure, superoxide activities of dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST)and levels of reduced glutathione (GSH) and malondialdehyde (MDA) were significantly increased, whereas the activity of glutathione peroxidase (GPx) significantly decreased and oxidative stress-related gene significantly changed. Liver lesions were mainly characterized by inflammatory cell infiltration, hepatocyte necrosis and fat vacuolation after exposure to Hg2+. Taken together, the results indicate that Hg2+ exposure leads to growth inhibition and oxidative stress in juvenile silver.

Protein and lipid growth rates regulate bioaccumulation of PCBs and Hg in Bighead Carp (Hypophthalmichthys nobilis) and Silver Carp (Hypophthalmichthys molitrix) from the Three Gorges Reservoir, China.

This study evaluated the effect of growth of different tissue compartments on the bioaccumulation of mercury (Hg) and polychlorinated biphenyls (PCBs) in Silver Carp (Hypophthalmichthys molitrix) and Bighead Carp (Hypophthalmichthys nobilis) from the Three Gorges Reservoir (TGR), China. A non-steady state bioenergetics/toxicokinetic model was developed to simulate PCB and Hg concentrations in these two species and compared with field data. Simulations using constant whole body growth rate and constant tissue to whole body weight ratios were contrasted against simulations adopting age specific whole body and tissue/age specific growth rates for their goodness of fit to field data. The simulations using age/tissue specific growth rates demonstrated better fit to field data for PCBs compared to the constant growth rate models (22% improved R2), while both models explained similar variation in Hg concentration data. Both species demonstrated higher growth rates of lipids (on a daily basis) relative to whole body and protein contributing to higher growth dilution of PCBs compared to Hg. Although stable isotope data indicated some degree of diet and/or habitat shift, simulations assuming a constant diet concentration explained between 36 and 40% of the variation in fish concentrations for both contaminants and fish species. This study demonstrates that differences in the bioaccumulation rate of PCBs and Hg by Asian carp can be partially explained by differences in the growth rates of key tissue storage compartments associated with each contaminant. These differences in chemical-specific growth dilution subsequently contribute to differences in chemical retention and bioaccumulation patterns of Hg and PCBs by fish.