Dynamic Changes of Selected Signaling Molecules in Ovaries Following Early-Life Exposure to Fumonisin B1 in Wistar Rats in Association With DNA Methylation.

RThe mycotoxin fumonisin B1 (FB1) poses a significant global problem due to its presence in the food chain. This study aimed to investigate the intergenerational effects of FB1 on epigenetic changes and the corresponding signaling pathways in rat ovaries. Specifically, we examined the expression levels of DNA methyl-transferase (Dnmt3b) and the Pi3kK/Akt/mTOR/Ampk pathway. Virgin Wistar albino female rats were divided into control and FB1 treatment (doses of 20 and 50 mg/kg body weight/day) groups and monitored from day 6 of pregnancy until delivery. Female rats from the first (F1) and second (F2) generations were euthanized at 4 weeks of age, and their ovaries were collected. In addition to histopathological damage, there was a significant dose-dependent increase in Dnmt3b protein in the ovaries of F1 females (p=0.0022 and p<0.0001, respectively), but not in those of F2 females. Furthermore, overexpression of the PI3K gene was observed only in the high-dose FB1 group in both the F1 and F2 generations. In F2, significant gene overexpression of Akt was observed in the high-dose FB1 group, while no effect was observed in F1. Both treated groups of F1 females showed significant repression of the mTOR gene, whereas no effect was observed in F2 females. In addition, FB1 did not have a significant effect on the expression of the Ampk gene in either treatment group in either generation. We conclude that early-life exposure to FB1 may directly impact the ovarian function of female rats by altering methylation patterns and Pi3k/Akt/mTOR pathway in first- generation females. However, this effect appears to be recoverable in the second-generation females. Key words Mycotoxin " Fumonisin B1 " Epigenetic " Signaling pathway " Methylation " Ovary.