22The aetiology of many gestational disorders is still unknown. However, insufficient trans-

Key points Inappropriate intake of key micronutrients in pregnancy is known to alter maternal endocrine status, impair placental development and induce fetal growth restriction. Selenium is an essential micronutrient required for the function of approximately 25 important proteins. However, the specific effects of selenium deficiency during pregnancy on maternal, placental and fetal outcomes are poorly understood. The present study demonstrates that maternal selenium deficiency increases maternal triiodothyronine and tetraiodothyronine concentrations, reduces fetal blood glucose concentrations, and induces fetal growth restriction. Placental expression of key selenium‐dependent thyroid hormone converting enzymes were reduced, whereas the expression of key placental nutrient transporters was dysregulated. Selenium deficiency had minimal impact on selenium‐dependent anti‐oxidants but increased placental copper concentrations and expression of superoxide dismutase 1. These results highlight the idea that selenium deficiency during pregnancy may contribute to thyroid dysfunction, causing reduced fetal growth, that may precede programmed disease outcomes in offspring. Abstract Selenium is a trace element fundamental to diverse homeostatic processes, including anti‐oxidant regulation and thyroid hormone metabolism. Selenium deficiency in pregnancy is common and increases the risk of pregnancy complications including fetal growth restriction. Although altered placental formation may contribute to these poor outcomes, the mechanism by which selenium deficiency contributes to complications in pregnancy is poorly understood. Female C57BL/6 mice were randomly allocated to control (>190 µg kg–1, n = 8) or low selenium (<50 µg kg–1, n = 8) diets 4 weeks prior to mating and throughout gestation. Pregnant mice were killed at embryonic day 18.5 followed by collection of maternal and fetal tissue. Maternal and fetal plasma thyroid hormone concentrations were analysed, as was placental expression of key selenoproteins involved in thyroid metabolism and anti‐oxidant defences. Selenium deficiency increased plasma tetraiodothyronine and triiodothyronine concentrations. This was associated with a reduction in placental expression of key selenodependent deiodinases, DIO2 and DIO3. Placental expression of selenium‐dependent anti‐oxidants was unaffected by selenium deficiency. Selenium deficiency reduced fetal glucose concentrations, leading to reduced fetal weight. Placental glycogen content was increased within the placenta, as was Slc2a3 mRNA expression. This is the first study to demonstrate that selenium deficiency may reduce fetal weight through increased maternal thyroid hormone concentrations, impaired placental thyroid hormone metabolism and dysregulated placental nutrient transporter expression. The study suggests that the magnitude of selenium deficiency commonly reported in pregnant women may be sufficient to impair thyroid metabolism but not placental anti‐oxidant concentrations.

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.

Mitochondria are central to cell function. The placenta forms the interface between maternal and fetal systems, and placental mitochondria have critical roles in maintaining pregnancy. The placenta is unusual in having two adjacent cell layers (cytotrophoblasts and the syncytiotrophoblast) with vastly different mitochondria that have distinct functions in health and disease. Mitochondria both produce the majority of reactive oxygen species (ROS), and are sensitive to ROS. ROS are important in allowing cells to sense their environment through mitochondrial-centred signalling, and this signalling also helps cells/tissues adapt to changing environments. However, excessive ROS are damaging, and increased ROS levels are associated with pregnancy complications, including the important disorders preeclampsia and gestational diabetes mellitus. Here we review the function of placental mitochondria in healthy pregnancy, and also in pregnancy complications. Placental mitochondria are critical to cell function, and mitochondrial damage is a feature of pregnancy complications. However, the responsiveness of mitochondria to ROS signalling may be central to placental adaptations that mitigate damage, and placental mitochondria are an attractive target for the development of therapeutics to improve pregnancy outcomes.

Placental function and homeostasis is very much dependent upon trophoblast mitochondria. Mitochondria are responsible for a myriad of functions including energy production, endocrine functions, nutrient and oxygen transfer as well as protecting the placenta from oxidative insult and cell stress. The materno-fetal interface is comprised of 2 related cell lineages, cytotrophoblast cells which fuse to form the overlaying syncytium. Mitochondrial morphology and function in these 2 lineages is different and, in this study, we describe methods for mitochondrial isolation, cryopreservation and preliminary biochemical characterisation of these discrete forms of mitochondria. Villous tissue was collected from normal term placentae following vaginal delivery (n=7). Differential centrifugation was used to isolate 2 fractions, larger mitochondria predominantly from the cytotrophoblast cells and smaller mitochondria from the syncytiotrophoblast. Freshly isolated mitochondria were assessed for Complex I and Complex II respiration and maximal respiratory capacity and these were compared to equivalent isolates that had been frozen, stored at-80 o C and revived. Other important functional parameters of mitochondrial activity were also assessed post cryopreservation including membrane potential, ATP production, progesterone biosynthesis and anti-oxidant expression. The methods described resulted in 2 mitochondrial populations which match the types of mitochondria observed in situ with election microscopy. Both forms of mitochondria were metabolically active and recovered well from cryopreservation. There were important functional differences between cyto-mitochondria and syncytio-mitochondria including decreased respiration, decreased oxidative phosphorylation, decreased anti-oxidant expression but increased expression of the enzyme CYP11A1 and increased progesterone production. This study highlights the need to consider different types of trophoblast mitochondria in placental studies and provides methods to facilitate this.