Genotype modulates gene expression profiles in the uterus in response to preconceptual folate supplementation.

Periconceptual supplementation of women with folate is considered a great success for public health. Higher folate status, either by supplementation, or via the mandatory fortification of grain products in the United States, has lead to significant reduction in the incidence of neural tube defects. Besides birth defects, folate deficiency has been linked to a variety of morbidities, most notably to increased risk for cancer. However, recent evidence suggests that excess folate may be detrimental - for birth defect incidence or in the progression of cancer. How folate mediates beneficial or detrimental effects is not well understood. It is also unknown what molecular responses are elicited in women taking folate supplements, and thus experience a bolus of folate on top of the status achieved by fortification. To characterize this response, we performed gene expression profiling experiments on uterus tissue of pregnant mice after a preconceptional regimen of supplementation with folinic acid. We suggest that folinic acid supplementation affects expression of genes that contribute to protein synthesis and localization, genes that play a role for mitochondrial biology and oxidative phosphorylation, and genes encoding nucleotide-binding proteins, including protein kinases and GTP-binding intracellular signaling factors. The extent of such a response is strongly modulated by the genetic background. Finally, we suggest that folinic acid supplementation in this paradigm may affect histone methylation status, a potential avenue to mechanisms of gene regulation.

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