Low Folate and Selenium in the Mouse Maternal Diet Alters Liver Gene Expression Patterns in the Offspring after Weaning

Abstract

During pregnancy, selenium (Se) and folate requirements increase, with deficiencies linked to neural tube defects (folate) and DNA oxidation (Se). This study investigated the effect of a high-fat diet either supplemented with (diet H), or marginally deficient in (diet L), Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis), methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring.

Reciprocal F1 hybrids of two inbred mouse strains reveal parent-of-origin and perinatal diet effects on behavior and expression

“…But it is conceivable that diet did in fact cause a systemic, diet-buffering change to the overall network of gene expression levels (MacNeil and Walhout. Indeed, our FDR numbers seem consistent with earlier work: in the few examples (to our knowledge) of FDR corrected results from previous rodent studies of perinatal diet effects on gene expression (Mortensen et al 2009; Altobelli et al 2013; Barnett et al 2015), 500-1000 genes were differentially expressed.…”

Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12‐dimethylbenz[a]anthracene‐induced mammary carcinogenesis in female rat offspring

“…Se has been shown to exert cell cycle regulatory effects in breast cancer cells and breast tumor‐bearing animals . In maternal intervention studies Se deficiency altered the expression of cell cycle control genes in the offspring's colonic tissue . On the other hand, the observation of decreased apoptosis in both Se‐DEF and Se‐SUP female offspring mammary glands suggests that this cellular process is not directly linked to increased breast cancer risk in the former group.…”

“…Although Se is essential in embryogenesis, few studies have evaluated its role in the developmental origins of health and disease (DOHaD) context. In rodents, maternal Se deficiency during gestation and lactation metabolically programmed the offspring and altered male offspring liver and colon gene expression with more pronounced effects when compared to post‐weaning Se deficiency, indicating timing of exposure as a key programming factor . Maternal Se supplementation during late gestation and lactation reduced spontaneous hepatomas in the rat male offspring .…”

The role of folic acid and selenium against oxidative damage from ethanol in early life programming: a review

“…Therefore, after administering ethanol to embryos and newborns, Se supplementation improves antioxidant profile in liver (Ojeda et al 2009a), kidney (Ojeda et al 2012) and heart, tissues which suffer high levels of Se depletion after ethanol exposure (Kalishwaralal et al 2015) (Figure 2). Barnett et al (2015) have found that in a high-fat maternal mouse diet during gestation and lactation, low folate (0.4ppm) and Se (0.08ppm) have stronger detrimental effects in offspring gene expression than the same diet fed to offspring post-weaning. This is related, among other factors, to methyl group metabolism.…”