Placental adaptations to micronutrient dysregulation in the programming of chronic disease

Hofstee, Pierre; McKeating, Daniel R.; Perkins, Anthony V.; Cuffe, James

doi:10.1111/1440-1681.12954

Cited by 29 publications

(53 citation statements)

References 125 publications

(180 reference statements)

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“…The recommended daily intake of selenium for Australia and New Zealand is ∼60 µg day –1 , increasing to 65 µg day –1 during pregnancy and 75 µg day –1 during lactation (NHMRC, ; Hofstee et al . ). Interestingly, several key studies suggest that doses greater than 100 µg/day may be required to minimize the risk of thyroid dysfunction (Stoffaneller & Morse, ).…”

Section: Discussionmentioning

confidence: 97%

“…We have previously stated the importance of controlling and clarifying the effects of single micronutrient deficits in pregnancy models (Hofstee et al . ; McKeating et al . ); however, we acknowledge that, in humans, there may be deficiencies in multiple micronutrients (Gernand et al .…”

Section: Discussionmentioning

confidence: 99%

“…Alterations to dietary selenium intake can disrupt multiple molecular pathways, especially when selenium demand increases, such as during pregnancy (Hofstee et al . ). Selenium deficiency has been associated with pregnancy disorders, including pre‐eclampsia, gestational diabetes mellitus (GDM), neural tube defects, fetal growth restriction and preterm birth (Richard et al .…”

Section: Introductionmentioning

confidence: 97%

“…In response to a decrease in selenium, other compensatory mechanisms may also prevent oxidative stress by increasing concentrations of other micronutrients, such as copper or zinc, which are important regulators of selenium independent anti‐oxidant systems (Hofstee et al . ). Alternatively, a decrease in these selenodependent anti‐oxidant proteins within the placenta may only occur when selenium concentrations are severely deficient.…”

Section: Introductionmentioning

confidence: 97%

“…Although less understood, it has been speculated that selenium deficiency may also impact a range of other hormones (Hofstee et al . ).…”

Section: Introductionmentioning

confidence: 97%

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Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth

Hofstee

Bartho

McKeating

et al. 2019

The Journal of Physiology

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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.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

“…Although less understood, it has been speculated that selenium deficiency may also impact a range of other hormones (Hofstee et al . ).…”

Section: Introductionmentioning

confidence: 97%

See 3 more Smart Citations

Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth

Hofstee

Bartho

McKeating

et al. 2019

The Journal of Physiology

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Circulating trace elements for the prediction of preeclampsia and small for gestational age babies

et al. 2021

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Poor gestational outcomes due to placental insufficiency can have lifelong consequences for mother and child. There is a need for better methods of diagnosis, and elemental metabolomics may provide a means to determine the risk of gestational disorders.This study used blood plasma samples collected at 36 weeks' gestation from women who later developed preeclampsia (n=38), or small-for-gestational age babies (n=91), along with matched controls (n=193). Multi-element analysis was conducted by inductively coupled plasma mass spectrometer (ICP-MS), allowing simultaneous measurement of 28 elements.Women who later developed PE, exhibited significantly increased concentrations of K, Rb and Ba. For SGA pregnancies, there was a significant in-crease in Cu and a decrease in As concentrations. Despite significant differences in single elements, the elemental profile of groups indicated no clustering of control, PE, or SGA samples. Positive predicative values correctly identified approximately 60% of SGA and 70% of PE samples. This is the first-time elemental metabolomics has been used to predict SGA and PE at 36 weeks. Though significant changes were identified, routine clinical use may be limited but may contribute to a multi marker test. Future analysis should include other biomarkers, metabolic data or clinical measurements made throughout gestation.

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Elemental Metabolomics for Prediction of Term Gestational Outcomes Utilising 18-Week Maternal Plasma and Urine Samples

McKeating

Clifton

Hurst

et al. 2020

Biol Trace Elem Res

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A normal pregnancy is essential to establishing a healthy start to life. Complications during have been associated with adverse perinatal outcomes and lifelong health problems. The ability to identify risk factors associated with pregnancy complications early in gestation is vitally important for preventing negative foetal outcomes. Maternal nutrition has been long considered vital to a healthy pregnancy, with micronutrients and trace elements heavily implicated in maternofoetal metabolism. This study proposed the use of elemental metabolomics to study multiple elements at 18 weeks gestation from blood plasma and urine to construct models that could predict outcomes such as small for gestational age (SGA) (n = 10), low placental weight (n = 18), and preterm birth (n = 13) from control samples (n = 87). Samples collected from the Lyell McEwin Hospital in Adelaide, South Australia, were measured for 27 plasma elements and 37 urine elements by inductively coupled plasma mass spectrometry. Exploratory analysis indicated an average selenium concentration 20 μg/L lower than established reference ranges across all groups, low zinc in preterm (0.64 μg/L, reference range 0.66-1.10 μg/L), and higher iodine in preterm and SGA gestations (preterm 102 μg/L, SGA 111 μg/L, reference range 40-92 μg/L). Using random forest algorithms with receiver operating characteristic curves, low placental weight was predicted with 86.7% accuracy using plasma, 78.6% prediction for SGA with urine, and 73.5% determination of preterm pregnancies. This study indicates that elemental metabolomic modelling could provide a means of early detection of at-risk pregnancies allowing for more targeted monitoring of mothers, with potential for early intervention strategies to be developed.

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Placental adaptations to micronutrient dysregulation in the programming of chronic disease

Cited by 29 publications

References 125 publications

Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth

Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth

Circulating trace elements for the prediction of preeclampsia and small for gestational age babies

Elemental Metabolomics for Prediction of Term Gestational Outcomes Utilising 18-Week Maternal Plasma and Urine Samples

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