Fumonisin FB 1 treatment acts synergistically with methyl donor deficiency during rat pregnancy to produce alterations of H 3‐ and H 4‐histone methylation patterns in fetuses

Scope Prenatal folate and methyl donor malnutrition lead to epigenetic alterations that could enhance susceptibility to disease. Methyl‐deficient diet ( MDD ) and fumonisin FB 1 are risk factors for neural tube defects and cancers. Evidence indicates that FB 1 impairs folate metabolism. Methods and results Folate receptors and four heterochromatin markers were investigated in rat fetuses liver derived from dams exposed to MDD and/or FB 1 administered at a dose twice higher than the provisional maximum tolerable daily intake (PMTDI = 2 μg/kg/day). Even though folate receptors transcription seemed up‐regulated by methyl depletion regardless of FB 1 treatment, combined MDD/FB 1 exposure might reverse this up‐regulation since folate receptors transcripts were lower in the MDD/FB 1 versus MDD group. Methyl depletion decreased H4K 20me3. Combined MDD/FB 1 decreased H4K 20me3 even more and increased H3K 9me3. The elevated H3K 9me3 can be viewed as a defense mechanism inciting the cell to resist heterochromatin disorganization. H3R 2me2 and H4K 16 A c varied according to this mechanism even though statistical significance was not consistent. Conclusion Considering that humans are exposed to FB 1 levels above the PMTDI , this study is relevant because it suggests that low doses of FB 1 interact with MDD thus contributing to disrupt the epigenetic landscape.