Abstract P226: Transcriptome Signature Of Placentas From Diabetic Pregnancies Is Confounded By Fetal Sex.

Abstract

Hypertension-associated obstetric diseases like diabetes mellitus (DM) or preeclampsia occur in 25-35% of pregnancies and are related to placental dysfunction. The placenta has a unique structure and function to guarantee healthy pregnancy, fetal development, and outcome. Thus, the diabetic environment featuring inflammation, metabolic alterations, and hypoxia, is challenging with increased stress for mother and foetus. Delivery-related complications and adverse post-pregnancy outcomes, for example the increased risk for preeclampsia, are related to placental pathology in the different types of DM. Therefore, understanding disturbed placental development during pathologic pregnancy is important. We hypothesize a placental transcriptome signature present in pathologic pregnancy. We aimed to broaden our understanding of placental adaptations to various forms of diabetic pregnancy. Human placenta samples from healthy controls (n = 29), women with gestational DM (GDM, n = 12), DM type 1 (DM1, n = 17), DM type 2 (DM2, n = 3) and GDM, DM1 or DM2 superimposed by preeclampsia (n = 16) were included. We quantified gene expression by Illumina TruSeq stranded total RNA Sequencing and analyzed data by means of principal component analysis (PCA), differential expression and gene set enrichment. The samples were mainly split by fetal sex in the PCA rather than diabetic subgroups. Genes associated with the principal components were primary located on the male sex chromosome ( Xist, Uty, Usp9y, Ddx3y ) and only weakly enriched in functionally relevant gene sets. The fetal sex was identified as single main explanatory variable when the principal components were associated with clinical patient data. Placentas complicated by DM2 identified 93 and 27 significant differential expressed genes (DEG; adj. p-value < 0.05) in comparison to healthy controls and GDM, respectively. Comparison of DM1 to DM2 or GDM showed four and two significant genes. In this cohort possible effects of GDM and preeclampsia were not observed.We conclude that fetal sex is dominating placental gene expression and confounding transcriptome signatures resulting from diabetes, in settings of well controlled diabetic disease.