LAUSR

Background: Pregnancies complicated by gestational diabetes (GDM) or maternal obesity (MOB) induce abnormal fetal development that can lead to diabetes and obesity later in life with sex specific manifestations. Alterations in miRNA expression in GDM and MOB exposed offspring and effects on development have not been fully described. Hypothesis: Exposure to an aberrant intrauterine milieu complicated by GDM and MOB leads to changes in miRNA and target gene expression in human fetal liver. Methods: Candidate miRNA expression was measured in second trimester AF from women diagnosed with GDM via multiplex miRNA assay (Firefly Bioworks, Abcam). Gene targets of differentially expressed miRNAs were determined from TargetScan and pathway enrichment determined via Ingenuity Pathway Analysis (IPA). MiRNA and target gene expression (mRNA and protein) were measured in a separate cohort of 2nd trimester primary human fetal hepatocytes (PHFH) exposed to MOB via QPCR and western blot. All studies were approved by UPENN and TEMPLE University IRBs. Results: GDM exposed AF had significant increases in miRNAs 199a-3p, 503-5p, and 1268a (p Conclusion: Our data suggest sex specific changes in miRNA and target gene expression in PHFH may be one mechanism responsible for sex specific metabolic changes in offspring exposed to GDM and obesity in utero. Disclosure A. Joshi: None. L. Goetzl: None. S.E. Pinney: None.