Elements are central to many cellular functions and enzymatic activities within living systems. Elemental metabolomics quantifies elements in biological samples, giving novel insight into how cellular processes are altered within disease states. The placenta is a highly metabolically active organ with numerous enzymatic functions that require elements. The aim of this project is to establish an elemental profile of placental mitochondria from cytotrophoblast (CT) and syncytiotrophoblast (ST), of healthy and gestational diabetes mellitus (GDM) pregnancies. We aim to translate these elemental profiles to investigate functional enzymatic changes.
CT and ST mitochondria were isolated from placental tissue collected from GDM (n=13) and matched control (n=10) pregnancies. Inductively coupled plasma mass spectrometry was utilised to create proteomic profiles of 65 elements. Superoxide dismutase (SOD) activity was measured by activity assay.
CT and ST mitochondria had distinct profiles within healthy pregnancies (16 different elements; p<0.05). In GDM, CT and ST mitochondria profiles were altered, with six additional elements (including Mn), distinguishing CT and ST mitochondria. 11 of the elements distinct between mitochondrial populations in healthy placentae were no longer different in GDM samples (p<0.05). Five elements, Ti, Cu, As, Zr, and Au, were distinct between CT and ST mitochondria in both healthy and GDM pregnancies (p<0.05). SOD activity was increased in GDM (p=0.01).
This research provides the foundation for the use of elemental metabolomics in the creation of translatable elemental profiles in placental tissue. Furthermore, this methodology allowed for differentiation between control and GDM samples in both CT and ST mitochondria. Differences observed in Mn and Cu through elemental profiling predicted a functional increase in SOD activity in GDM. This study shows the translatable potential of elemental metabolomics in characterising and predicting functional alterations between mitochondrial populations in gestational disorders.