Trace elements are important for human health and development. The body requires specific micronutrients to function, with aberrant changes associated with a variety of negative health outcomes. Despite this evidence, the status and function of micronutrients during pregnancy are relatively unknown and more information is required to ensure that women receive optimal intakes for foetal development. Changes in trace element status have been associated with pregnancy complications such as gestational diabetes mellitus (GDM), pre-eclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth. Measuring micronutrients with methodologies such as elemental metabolomics, which involves the simultaneous quantification and characterisation of multiple elements, could provide insight into gestational disorders. Identifying unique and subtle micronutrient changes may highlight associated proteins that are affected underpinning the pathophysiology of these complications, leading to new means of disease diagnosis. This review will provide a comprehensive summary of micronutrient status during pregnancy, and their associations with gestational disorders. Furthermore, it will also comment on the potential use of elemental metabolomics as a technique for disease characterisation and prediction.

The levels of trace elements in whole blood and plasma have been widely used for assessing nutritional status and monitoring exposure and can vary widely in populations from different geographical regions. In this study, whole blood samples (n = 120) and plasma samples (n = 120) were obtained from healthy donors attending the Red Cross Blood Bank (Queensland Red Cross Blood Service), which provided information for age and sex. There were 71 males (age range: 19–73 years) and 49 females (age range: 18–72 years) for whole blood samples, and 59 males (age range: 19–81 years) and 61 females (age range: 19–73 years) for plasma samples. The main aim of the study was to provide information on blood reference levels of 21 trace elements (Ag, Al, As, Bi, Br, Cd, Co, Cr, Cu, Hg, I, Mn, Mo, Ni, Pb, Sb, Se, Tl, U, V, Zn) in Queensland. The study also aimed to assess differences in trace element blood levels between males and females and the effect of age. The trace element levels in blood samples were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and the standard reference materials of Seronorm (Trace Elements Whole Blood) and UTAK (Trace Elements Serum) were used for quality control and assurance. The study found wide variations of trace element levels in whole blood and plasma, and generally the levels were comparable to other countries. No detectable levels were found for Bi, Cr, U and V in whole blood, but V levels were found in plasma samples. There were significant differences between males and females for whole blood Cu (p < 0.001), I (p = 0.009), Tl (p = 0.016) and Zn (p = 0.016). Significant differences were also found for plasma Cu (p < 0.001) and Se (p = 0.003) between males and females. There were trends of increased levels of blood Pb, Se and Zn with age. The study has provided further information on a wide range of trace elements in blood as reference levels for Queensland and Australia which are currently lacking.

As gestation proceeds the human placenta is in a constant state of renewal and placental debris is released into the maternal circulation where it can trigger adverse physiological and immunological responses. Trophoblast cells of the placenta differentiate from mononuclear cytotrophoblast cells to fuse and form the syncytiotrophoblast, a multinuclear layer that covers the entire surface of the placenta. As part of this process there are significant changes to cellular cytoskeletal organization and organelle morphology. In this study we have examined the molecular changes that occur in mitochondria from these two cellular compartments and identified differential expression of key proteins that underpin changes in mitochondrial morphology, metabolism and function. Mitochondria were isolated for term placental tissue and separated according to size and density by sequential differential centrifugation. Isolated mitochondrial populations were then subjected to proteomics using HPLC separation of peptides and MS identification. Differential expression of proteins of interest was confirmed by western blots. Using a bioinformatics approach we also examined published protein databases to confirm our observations. In total 651 proteins were differentially regulated in mitochondria from cytotrophoblast versus syncytiotrophoblast. Of these 29 were statistically significant and chosen for subsequent analysis. These included subunits of ATP synthase that would affect ATP production and cristae structure, carbohydrate metabolizing enzymes phospoenolpyruvate carboxykinase-2, pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH), fatty acid metabolizing enzyme acyl-CoA dehydrogenase, stress responses such a glucose regulated protein-78 and protein disulfide isomerase, and mitochondrial dynamics proteins mitofusin 1 and 2. Placental cell biology and mitochondrial function is central to the pathogenesis of many gestational disorders such as preeclampsia, pre-term birth, fetal growth restriction and gestational diabetes. These studies show important shifts in mitochondrial metabolism and dynamics post trophoblast differentiation and provide key molecular targets for study in pathological pregnancies.