Fumonisin FB1 treatment acts synergistically with methyl donor deficiency during rat pregnancy to produce alterations of H3- and H4-histone methylation patterns in fetuses.
METHODS
Prenatal folate and methyl donor malnutrition lead to epigenetic alterations that could enhance susceptibility to disease. Methyl-deficient diet (MDD) and fumonisin FB1 are risk factors for neural tube defects and cancers. Evidence indicates that FB1 impairs folate metabolism.


RESULTS
Folate receptors and four heterochromatin markers were investigated in rat fetuses liver derived from dams exposed to MDD and/or FB1 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 FB1 treatment, combined MDD/FB1 exposure might reverse this up-regulation since folate receptors transcripts were lower in the MDD/FB1 versus MDD group. Methyl depletion decreased H4K20me3. Combined MDD/FB1 decreased H4K20me3 even more and increased H3K9me3. The elevated H3K9me3 can be viewed as a defense mechanism inciting the cell to resist heterochromatin disorganization. H3R2me2 and H4K16Ac varied according to this mechanism even though statistical significance was not consistent.


CONCLUSIONS
Considering that humans are exposed to FB1 levels above the PMTDI, this study is relevant because it suggests that low doses of FB1 interact with MDD thus contributing to disrupt the epigenetic landscape.
INSERM U954 Nutrition, Genetics, and Environmental Risk Exposure, Faculté de Médecine, Nancy Université, Vandoeuvre les Nancy, France.
Hélène
H
Pellanda
Thierry
T
Forges
Aude
A
Bressenot
Abalo
A
Chango
Jean-Pierre
JP
Bronowicki
Jean-Louis
JL
Guéant
Fares
F
Namour
D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002796:Choline Deficiency / Q000150:complications / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D005234:Fatty Liver / Q000209:etiology; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000150:complications / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D058972:Folic Acid Transporters / Q000235:genetics / Q000378:metabolism; D037341:Fumonisins / Q000008:administration & dosage / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006570:Heterochromatin / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D039382:Maternal Nutritional Physiological Phenomena; D008745:Methylation / Q000187:drug effects; D009436:Neural Tube Defects / Q000139:chemically induced / Q000209:etiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000633:toxicity*; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000196:embryology / Q000378:metabolism / Q000473:pathology
D058972:Folic Acid Transporters; D037341:Fumonisins; D006570:Heterochromatin; D006657:Histones; D012333:RNA, Messenger; D013723:Teratogens; C056933:fumonisin B1; D005492:Folic Acid