111: Does your placenta know you're diabetic? A study in placental gene expression

Trends in diagnosis and management of gestational diabetes continually change as we learn more about downstream effects on both mother and fetus. We hypothesized that given the placenta's crucial function in glucose uptake and metabolism, if gestational diabetes is a unique clinical entity and not simply a manifestation of pregnancy physiology or undiagnosed pre-gestational diabetes, we should detect unique molecular signature differences in placental gene expression. This study was therefore designed to rigorously examine placental gene expression of gestational and pre-gestational diabetics. Namely, the aim of this work is to differentiate true pathology from a potentially normal physiologic state of pregnancy. Whole transcriptome RNA sequencing was performed on placentas from subjects with pre-gestational diabetes (T2DM), gestational diabetes (GDMA), and non-diabetic controls (N=38) with computational analysis for differential gene expression and gene pathway enrichment. RT-qPCR (N=145) was used to validate selected genes with p<0.05 by analysis of variance (ANOVA) considered statistically significant. Comparison of the placental transcriptome of diabetic and non-diabetic gravidae revealed 5407 differentially expressed genes (q<0.05), with substantial overlap between GDMA and T2DM (1a). Placental expression of PER1, SOGA1, DOCK5, and IL2RB differed significantly among groups (1b). Subjects clustered by diabetic status (2a), with significantly altered metabolic gene pathways (2b,c). Importantly, there was no significant difference in gene expression between GDMA2 and T2DM in genes selected for further investigation by RT-qPCR. Postpartum screening (71.3% compliance) revealed a 7.3% diagnosis of T2DM. Changes in placental gene expression between diabetic subjects and controls revealed a portion of differentially expressed genes shared between diabetic subtypes, with a set of genes specific to each disease. This unique expression pattern supports the supposition that gestational and pre-gestational diabetes are distinct entities with individualized placental signatures. Indeed, post-pregnancy assessment verified our initial diabetes classification, with a low rate of T2DM diagnosis among GDMA subjects. Together, these data demonstrate a robust and specific placental response to maternal diabetic status.View Large Image Figure ViewerDownload Hi-res image Download (PPT)