Maternal exposure to iron oxide nanoparticles is associated with ferroptosis in the brain: A chicken embryo model analysis.

Ferroptosis is a form of cell death associated with iron-dependent lipid peroxidation. We used a chicken embryo model to investigate if ferroptosis was implicated in the molecular mechanism underlying the potential effects of maternal exposure to iron oxide nanoparticles (IONPs) on the developing brain. One hundred and eighty fertilized eggs were randomly divided into six groups (30 eggs/group; 10 eggs/replicate). Groups I and II received maghemite (γ-Fe2 O3 ) NPs (MGMNPs), while groups III and IV received magnetite (Fe3 O4 ) NPs (MGTNPs). Both MGMNP and MGTNP were administrated at the concentrations of 100 and 250 ppm. One group (placebo) received saline, and the other remained untreated (control). The compounds were given by in ovo method (0.3 ml/egg) only once on the first day of the embryonic period. Samples from cerebral tissue were collected on day 20 for histopathological, biochemical and gene expression analyses. Total antioxidant capacity (TAC) and malondialdehyde (MDA) increased; glutathione peroxidase (GPX) expression and activity decreased in IONPs-treated groups. Ferroptotic cells appeared in the cerebral tissue following exposure to the low dose of MGMNP and MGTNP. Oxidative stress and ferroptotic cells were more evident for MGMNP compared to MGTNP. The low dose of MGMNP and MGTNP induced more severe oxidative stress in the cerebral tissue. According to the results, maternal exposure to IONPs is associated with ferroptosis in the brain. This work could encourage future researches to investigate inhibitors of ferroptosis as a protective strategy against iron-induced cell injuries and cell death.

Differential expression of small heat shock proteins in the brain of broiler embryo; the effects of embryonic thermal manipulation.

Broilers are more vulnerable to high temperatures than mammals due to the feather cover, lack of sweat glands, fast growth and intensive breeding in commercial systems. Thermal stresses affect the function of various organs and change the expression profiles of hundreds of genes in the different tissues of broilers. Thermal manipulation (TM) during embryogenesis can increase heat tolerance in growing broilers. Small heat shock proteins (SHSPs) are a group of HSPs which participate in many cellular functions like response to different stressors. However, their role in the thermotolerance has not been fully elucidated. Ninety fertilized eggs were randomly divided into three groups (30 eggs/group; 10 eggs/replicate). Normal control (NC) eggs were incubated at 37.5 °C throughout the incubation period whereas heat stress (HS) and cold stress (CS) groups were kept at 41 °C and 33 °C from 15 to 17th day of incubation for 3 h each day, respectively. On day 20, samples from the cerebrums were harvested for histopathology and mRNA expression analyses of HSPB1, HSPB5, HSPB8, and HSPB9. There were no significant differences in survivability, defected embryos, hatchability, and body weight among treatments. TM had no major deleterious effects on the cerebral tissue except for mild degeneration in the HS group. HSPB1, HSPB5, HSPB8, and HSPB9 were expressed in the presence and absence of TM. All SHSP genes tested were downregulated in response to TM except for HSPB9 which was upregulated in the HS group. The highest change in gene expression due to TM observed for HSPB1. This study presents a broader understanding of mechanisms underlying response to TM in broilers. The results suggest that HSPB1, HSPB5, HSPB8, and HSPB9 are involved in thermotolerance in broilers and SHSPs could be involved in the gene expression profiling of TM. It may propose the use of nutritional supplements in the poultry industry to modulate SHSPs.

Small Heat Shock Protein's Gene Expression Response to Iron Oxide Nanoparticles in the Brain.

Small heat shock proteins (SHSPs) are conserved proteins that participate in many cellular functions like preventing protein aggregation and stress response. However, their role in responding to nanoparticles (NPs) has not yet been explained. We used a chicken embryo model to investigate the effects of two different forms of iron oxide-NPs (IONPs) on the mRNA expression of HSPB1, HSPB5, HSPB8, and HSPB9 in cerebral tissue. Two hundred-ten fertilized eggs were randomly divided into seven groups (30 eggs/group; 10 eggs/replicate). Three groups received 100 ppm, 250 ppm, and 500 ppm of Fe2O3-NPs, respectively. Three other groups received 100 ppm, 250 ppm, and 500 ppm of Fe3O4-NPs, respectively, and one group remained untreated as a control. The NPs were given by in ovo method (0.3 ml/egg) only once on the first day of the embryonic period. Samples from cerebrums were collected on day 20 for gene expression analyses. HSPB1, HSPB5, HSPB8, and HSPB9 were all expressed in both normal and IONPs exposed cerebrums. SHSPs tested were differentially expressed in response to various concentrations of IONPs. The highest expression levels in response to Fe2O3-NPs and Fe3O4-NPs were observed for HSPB5 and HSPB9, respectively. The greatest gene expression changes due to the Fe2O3-NPs and Fe3O4-NPs exposure observed for HSPB1 and HSPB5, respectively. The results suggest a protective cellular mechanism against IONPs through SHSPs and recommend that expression profiling of SHSPs be included in the study of nanotoxicity.