Maternal diet modulates placental nutrient transporter gene expression in a mouse model of diabetic pregnancy

Abstract

Diabetes in the mother during pregnancy is a risk factor for birth defects and perinatal complications and can affect long-term health of the offspring through developmental programming of susceptibility to metabolic disease. We previously showed that Streptozotocin-induced maternal diabetes in mice is associated with altered cell differentiation and with smaller size of the placenta. Placental size and fetal size were affected by maternal diet in this model, and maternal diet also modulated the risk for neural tube defects. In the present study, we sought to determine the extent to which these effects might be mediated through altered expression of nutrient transporters, specifically glucose and fatty acid transporters in the placenta. Our results demonstrate that expression of several transporters is modulated by both maternal diet and maternal diabetes. Diet was revealed as the more prominent determinant of nutrient transporter expression levels, even in pregnancies with uncontrolled diabetes, consistent with the role of diet in placental and fetal growth. Notably, the largest changes in nutrient transporter expression levels were detected around midgestation time points when the placenta is being formed. These findings place the critical time period for susceptibility to diet exposures earlier than previously appreciated, implying that mechanisms underlying developmental programming can act on placenta formation.

Nutrient Transporter Gene Expression in the Early Conceptus—Implications From Two Mouse Models of Diabetic Pregnancy

“…Blood glucose levels in NOD females over the age of 12 weeks were monitored weekly; once the levels were greater than 250 mg/dl, the females were considered diabetic, and were mated to normoglycemic NOD male mice. Hyperglycemia was induced in FVB/N females after 8 weeks of age by Streptozotocin injection as described previously ( Kappen et al, 2011 ; Salbaum et al, 2011 ; Kappen et al, 2012 ; Kappen et al, 2019 ). All mice were housed in specific pathogen-free conditions, and were fed Purina 5,001 chow diet.…”

“…Where possible, the amplicon was designed to span across an exon-exon boundary to exclude amplification from potential contamination with genomic DNA. The locations and sequences of primers have been published ( Kappen et al, 2019 ). Synthesis of the primer sets was carried out by IDT (Integrated DNA Technologies, Coralville, IA).…”

Effects of Maternal Diabetes and Diet on Gene Expression in the Murine Placenta

“…The blood glucose levels and morphometric parameters of pregnant dams have been published [ 11 , 12 ]. Archived placenta samples were used in the present study that had been collected and processed for RNA extraction as published, and quantitative PCR was performed exactly as before [ 11 , 12 , 17 , 18 ].…”

“…Our method for quantitation of gene expression levels was applied exactly as in previous studies [ 11 , 12 , 17 , 18 ]. Measurements on each sample were done in triplicates and obtained values were averaged.…”

“…Amplification efficiencies were calculated, and statistical evaluation was performed on ∆C T values. Experimental groups consisted of six placentae, each from a separate diabetic or control pregnancy, respectively [ 12 , 18 ]. Figures show inverse ∆C T to depict the highest expression as the highest visual points on the graphs.…”