Transgenerational inheritance of methylmercury and vitamin A-induced toxicological effects in a Wistar rats environmental-based model.

Mercury (Hg) and vitamin A (VitA) are two environmental factors with potential health impacts, especially during pregnancy and early childhood. Fish and seafood may present elevated levels of methylmercury (MeHg), the major Hg derivative, and VitA. This study aimed to evaluate the transgenerational effects of exposure to MeHg and/or VitA on epigenetic and toxicological parameters in a Wistar rat model. Our findings revealed persistent toxicological effects in generations F1 and F2 following low/mild doses of MeHg and/or VitA exposure during dams' (F0) gestation and breastfeeding. Toxicological effects observed in F2 included chronic DNA damage, bone marrow toxicity, altered microglial content, reduced neuronal signal, and diminished male longevity. Sex-specific patterns were also observed. Co-exposure to MeHg and VitA showed both synergistic and antagonistic effects. Additionally, the study demonstrated that MeHg and VitA affected histone methylation and caused consistent effects in F2. While MeHg exposure has been associated with transgenerational inheritance effects in other organisms, this study provides the first evidence of transgenerational inheritance of MeHg and VitA-induced toxicological effects in rodents. Although the exact mechanism is not yet fully understood, these findings suggest that MeHg and VitA may perpetuate their impacts across generations. The study highlights the need for remedial policies and interventions to mitigate the potential health problems faced by future generations exposed to MeHg or VitA. Further research is warranted to investigate the transgenerational effects beyond F2 and determine the matrilineal or patrilineal inheritance patterns.

Effects of foetal and breastfeeding exposure to methylmercury (MeHg) and retinol palmitate (Vitamin A) in rats: Redox parameters and susceptibility to DNA damage in liver.

Methylmercury (MeHg) is known to be a chemical that poses a risk to public health. Exposure to MeHg and vitamin A (VitA) occurs through the ingestion of fish, present in the diet of most pregnant women. The absorption of these elements generates oxidative stress and can generate adaptations for future stressful events. Here, we assessed how exposure to VitA and/or MeHg during the fetal and breastfeeding period modulates the toxicity of MeHg reexposure in adulthood. We focus on redox systems and repairing DNA damage. Male rats (n = 50), were divided into 5 groups. Control received mineral oil; The VitA group received VitA during pregnancy, during breastfeeding and was exposed to MeHg in adulthood; VitA + MeHg received VitA and MeHg during pregnancy and breastfeeding and was exposed to MeHg in adulthood. The single exposure group (SE) was exposed to MeHg only in adulthood; and the MeHg group was pre-exposed to MeHg during pregnancy and breastfeeding and re-exposed to MeHg in adulthood. After treating the animals, we evaluated the redox status and the level of DNA damage in all rats. The results revealed that MeHg significantly decreased the activity of glutathione peroxidase (GPx) and sulfhydryl levels and increased the activity of superoxide dismutase (SOD), glutathione transferase, glutathione and carbonyl in all exposed groups. These results suggest that the second exposure to MeHg directly altered the effects of oxidation and that there were no specific effects associated with exposure during the fetal and breastfeeding periods. In addition, our findings indicate that MDA levels increased in MeHg and SE levels and no differences in MDA levels were observed between the VitA and MeHg + VitA groups. We also observed that animals pretreated exclusively with VitA showed residual damage similar to the control's DNA, while the other groups showed statistically higher levels of damage. In conclusion, low doses of MeHg and VitA during fetal and breastfeeding periods were unable to condition an adaptive response to subsequent exposure to MeHg in adulthood in relation to the observed levels of oxidative damage assessed after exposure.

Hepatic and neurobiological effects of foetal and breastfeeding and adulthood exposure to methylmercury in Wistar rats.

Methylmercury (MeHg) is an organic bioaccumulated mercury derivative that strongly affects the environment and represents a public health problem primarily to riparian communities in South America. Our objective was to investigate the hepatic and neurological effects of MeHg exposure during the phases foetal and breast-feeding and adult in Wistar rats. Wistar rats (n = 10) were divided into 3 groups. Control group received mineral oil; The simple exposure (SE) group was exposed only in adulthood (0.5 mg/kg/day); and double exposure (DE) was pre-exposed to MeHg 0.5 mg/kg/day during pregnancy and breastfeeding (±40 days) and re-exposed to MeHg for 45 days from day 100. After, we evaluated possible abnormalities. Behavioral and biochemical parameters in liver and occipital cortex (CO), markers of liver injury, redox and AKT/GSK3ß/mTOR signaling pathway. Our results showed that both groups treated with MeHg presented significant alterations, such as decreased locomotion and exploration and impaired visuospatial perception. The rats exposed to MeHg showed severe liver damage and increased hepatic glycogen concentration. The MeHg groups showed significant impairment in redox balance and oxidative damage to liver macromolecules and CO. MeHg upregulated the AKT/GSK3ß/mTOR pathway and the phosphorylated form of the Tau protein. In addition, we found a reduction in NeuN and GFAP immunocontent. These results represent the first approach to the hepatotoxic and neural effects of foetal and adult MeHg exposure.