My research focuses on the effects obese pregnancies complicated by gestational diabetes mellitus (GDM) have on the offspring, and how treatment with metformin, a glucose-lowering drug, affects the offspring’s health later in life through placental extracellular vesicles (EVs). Metformin crosses the placenta and fetal metformin concentrations can vary from 50% to the same level as the concentration in maternal plasma. Despite metformin’s beneficial effects on the mother, detrimental effects on the fetus have been observed such as an impaired cardiometabolic phenotype later in late due to postnatal catch-up growth. Placental EVs and their content are a means of communication between the mother and the fetus and play an important role in maintaining a healthy pregnancy. EVs contain and transport cellular cargo such as phospholipids, miRNA, mRNA, DNA, transmembrane and cytosolic proteins, which can regulate physiological and pathological processes when interacting with a specific cell. It has been shown that both the number of EVs and their miRNA content is influenced by obstetric complications such as GDM and pre-eclampsia. Therefore, by using a well-established GDM mouse model, primary human trophoblasts and trophoblast organoids, my project aims to identify the effects of hyperglycaemia and metformin on EVs and their content (miRNAs and protein), as well as their role in mediating the detrimental effects on the offspring. I have a strong interest in EVs and miRNAs in the context of developmental programming.
