Endocrine Abstracts

Diabetes during pregnancy is associated with short- and long-term health complications for both mother and offspring, such as cardiometabolic diseases, that are possibly linked to changes in placental development and function. High-throughput experiments can help uncover disease mechanisms, but there is no consensus on the specific molecular changes that occur in diabetic placentas. We conducted a systematic review of the literature to identify commonalities and thus determine which pathways are most frequently affected by maternal diabetes. A systematic literature search was conducted in PubMed to identify studies that performed high-throughput experiments comparing placental tissue or cells from diabetic and uncomplicated pregnancies. Screens were conducted on all types of high-throughput molecular methodologies, however due to limited published studies in other areas, only studies examining changes in protein and RNA level were included in subsequent analyses. Annotation conversion to gene names was performed in g:Convert to identify commonly dysregulated RNA and protein levels and g:GOST was used for functional profiling of individual study datasets and of RNAs and proteins list with same directional changes. From the 56 studies initially identified, the majority (n = 41) investigated protein (n = 12) or RNA abundance (n = 29) in gestational diabetes mellitus (GDM). A total of 15 common differentially abundant proteins (DAPs) and 414 differentially expressed genes (DEGs) were identified in at least two separate studies, with 8 DAPs and 189 DEGs exhibiting a consistent directional change. Functional profiling of individual studies’ list and the list of 189 DEGs, demonstrated that pathways associated with coagulation, MAPK, Wnt, IGFBP, TGFB signalling, and several immune and vascular processes were consistently altered in GDM placentas. This study identified key molecular and cellular changes that occur in GDM placentas. Whilst further research is required, the identified changes could serve as therapeutic targets to improve maternal and fetal outcomes in GDM.