Publications by authors named "Anthony V Perkins"

64 Publications

The Placental Ferroxidase Zyklopen Is Not Essential for Iron Transport to the Fetus in Mice.

J Nutr 2021 Jun 10. Epub 2021 Jun 10.

Molecular Nutrition Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia.

Background: The ferroxidase zyklopen (Zp) has been implicated in the placental transfer of iron to the fetus. However, the evidence for this is largely circumstantial.

Objectives: This study aimed to determine whether Zp is essential for placental iron transfer.

Methods: A model was established using 8- to 12-wk-old pregnant C57BL/6 mice on standard rodent chow in which Zp was knocked out in the fetus and fetal components of the placenta. Zp was also disrupted in the entire placenta using global Zp knockout mice. Inductively coupled plasma MS was used to measure total fetal iron, an indicator of the amount of iron transferred by the placenta to the fetus, at embryonic day 18.5 of gestation. Iron transporter expression in the placenta was measured by Western blotting, and the expression of Hamp1, the gene encoding the iron regulatory hormone hepcidin, was determined in fetal liver by real-time PCR.

Results: There was no change in the amount of iron transferred to the fetus when Zp was disrupted in either the fetal component of the placenta or the entire placenta. No compensatory changes in the expression of the iron transport proteins transferrin receptor 1 or ferroportin were observed, nor was there any change in fetal liver Hamp1 mRNA. Hephl1, the gene encoding Zp, was expressed mainly in the maternal decidua of the placenta and not in the nutrient-transporting syncytiotrophoblast. Disruption of Zp in the whole placenta resulted in a 26% increase in placental size (P < 0.01).

Conclusions: Our data indicate that Zp is not essential for the efficient transfer of iron to the fetus in mice and is localized predominantly in the maternal decidua. The increase in placental size observed when Zp is knocked out in the entire placenta suggests that this protein may play a role in placental development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jn/nxab174DOI Listing
June 2021

Temporal changes in blood oxidative stress biomarkers across the menstrual cycle and with oral contraceptive use in active women.

Eur J Appl Physiol 2021 Jun 9. Epub 2021 Jun 9.

Griffith Sports Science, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.

Purpose: To examine the temporal changes in blood oxidative stress biomarkers in recreationally-trained women that were naturally-cycling (WomenNC) or using oral contraceptives (WomenOC) across one month.

Methods: Blood samples were acquired at three timepoints of the menstrual cycle (1: early-follicular, 2: late-follicular and 3: mid-luteal) and oral contraceptive packet (1: InactiveOC, 2: Mid-activeOC and 3: Late-activeOC) for determination of estradiol, progesterone, oxidative stress, C-reactive protein (CRP) and other cardiometabolic biomarkers in plasma and serum.

Results: There was a Group by Time effect on estradiol (p < 0.001, partial η = 0.64) and progesterone (p < 0.001, partial η = 0.77). Malondialdehyde, lipid hydroperoxides and CRP concentrations were higher in WomenOC during Late-activeOC compared to InactiveOC (+ 96%, + 23% and + 104%, respectively, p < 0.05). However, there were no changes in these biomarkers across the menstrual cycle in WomenNC (p > 0.05). At all timepoints (i.e., 1, 2 and 3), WomenOC had elevated lipid hydroperoxides (+ 28, + 48% and + 50%) and CRP (+ 71%, + 117% and + 130%) compared to WomenNC (p < 0.05, partial η > 0.25). There was no Group by Time effect on non-enzymatic antioxidants or glutathione peroxidase; however, glutathione peroxidase was lower in WomenOC, i.e., main effect of group (p < 0.05, partial η > 0.20).

Conclusion: These findings demonstrate that WomenOC not only have higher oxidative stress and CRP than WomenNC, but also a transient increase across one month of habitual oral contraceptive use. Since changes in oxidative stress and CRP often relate to training stress and recovery, these outcomes may have implications to workload monitoring practices in female athletes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00421-021-04734-0DOI Listing
June 2021

Maternal diet high in linoleic acid alters offspring fatty acids and cardiovascular function in a rat model.

Br J Nutr 2021 Apr 16:1-14. Epub 2021 Apr 16.

Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia.

Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and its relationship to circulating FA and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1·44 % energy from LA) or high LA (HLA; 6·21 % energy from LA) diets for 10 weeks before pregnancy and during gestation/lactation. Offspring, weaned at postnatal day 25, were fed LLA or HLA diets and euthanised at postnatal day 40 (n 6-8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. α-Linolenic acid (ALA) and EPA were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic pressure-volume relationship (PVR), and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after occlusion. Thus, maternal HLA diets impact lipids, FA and cardiac function in offspring, with postnatal diet modifying FA and cardiac function in the female offspring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0007114521001276DOI Listing
April 2021

Trace Element Analysis in Whole Blood and Plasma for Reference Levels in a Selected Queensland Population, Australia.

Int J Environ Res Public Health 2021 03 6;18(5). Epub 2021 Mar 6.

Queensland Health Forensic and Scientific Services, Coopers Plains, QLD 4108, Australia.

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 ( = 120) and plasma samples ( = 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 ( < 0.001), I ( = 0.009), Tl ( = 0.016) and Zn ( = 0.016). Significant differences were also found for plasma Cu ( < 0.001) and Se ( = 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18052652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967308PMC
March 2021

Maternal and Postnatal High Linoleic Acid Diet Impacts Lipid Metabolism in Adult Rat Offspring in a Sex-Specific Manner.

Int J Mol Sci 2021 Mar 14;22(6). Epub 2021 Mar 14.

Institute for Health and Sport, Victoria University, Melbourne, VIC 8001, Australia.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal high LA (HLA) diet on plasma FA composition, plasma and hepatic lipids and genes involved in lipid metabolism in the liver of adult offspring. Female rats were fed with low LA (LLA; 1.44% LA) or HLA (6.21% LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed either LLA or HLA diets and sacrificed at PN180. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. Maternal HLA diet increased circulating leptin in female offspring, but not in males. Maternal HLA diet decreased circulating adiponectin in males. Postnatal HLA diet significantly decreased aspartate transaminase (AST) in females and downregulated total cholesterol, HDL-cholesterol and triglycerides in the plasma of males. Maternal HLA diet downregulated the hepatic mRNA expression of in both male and female offspring and decreased the hepatic mRNA expression of and in females. Both maternal and postnatal HLA diet decreased hepatic mRNA expression of in females. Postnatal diet significantly altered circulating fatty acid concentrations, with sex-specific differences in genes that control lipid metabolism in the adult offspring following exposure to high LA diet in utero.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22062946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999727PMC
March 2021

Maternal selenium deficiency in mice promotes sex-specific changes to urine flow and renal expression of mitochondrial proteins in adult offspring.

Physiol Rep 2021 Mar;9(6):e14785

School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.

Selenium deficiency during pregnancy can impair fetal development and predispose offspring to thyroid dysfunction. Given that key selenoproteins are highly expressed in the kidney and that poor thyroid health can lead to kidney disease, it is likely that kidney function may be impaired in offspring of selenium-deficient mothers. This study utilized a mouse model of maternal selenium deficiency to investigate kidney protein glycation, mitochondrial adaptations, and urinary excretion in offspring. Female C57BL/6 mice were fed control (>190 µg selenium/kg) or low selenium (<50 µg selenium/kg) diets four weeks prior to mating, throughout gestation, and lactation. At postnatal day (PN) 170, offspring were placed in metabolic cages for 24 hr prior to tissue collection at PN180. Maternal selenium deficiency did not impact selenoprotein antioxidant activity, but increased advanced glycation end products in female kidneys. Male offspring had reduced renal Complex II and Complex IV protein levels and lower 24 hr urine flow. Although renal aquaporin 2 (Aqp2) and arginine vasopressin receptor 2 (Avpr2) mRNA were not altered by maternal selenium deficiency, a correlation between urine flow and plasma free T concentrations in male but not female offspring suggests that programed thyroid dysfunction may be mediating impaired urine flow. This study demonstrates that maternal selenium deficiency can lead to long-term deficits in kidney parameters that may be secondary to impaired thyroid dysfunction. Considering the significant burden of renal dysfunction as a comorbidity to metabolic diseases, improving maternal selenium intake in pregnancy may be one simple measure to prevent lifelong disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.14785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995548PMC
March 2021

Effect of Selenium and Iodine on Oxidative Stress in the First Trimester Human Placenta Explants.

Nutrients 2021 Feb 28;13(3). Epub 2021 Feb 28.

School of Agriculture, Food and Wine, Waite Research Institute, and Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia.

Imbalanced maternal micronutrient status, poor placentation, and oxidative stress are associated with greater risk of pregnancy complications, which impact mother and offspring health. As selenium, iodine, and copper are essential micronutrients with key roles in antioxidant systems, this study investigated their potential protective effects on placenta against oxidative stress. First trimester human placenta explants were treated with different concentrations of selenium (sodium selenite), iodine (potassium iodide), their combination or copper (copper (II) sulfate). The concentrations represented deficient, physiological, or super physiological levels. Oxidative stress was induced by menadione or antimycin. Placenta explants were collected, fixed, processed, and embedded for laser ablation inductively coupled plasma-mass spectrometry (LA ICP-MS) element imaging or immunohistochemical labelling. LA ICP-MS showed that placenta could uptake selenium and copper from the media. Sodium selenite and potassium iodide reduced DNA damage and apoptosis ( < 0.05). Following oxidative stress induction, a higher concentration of sodium selenite (1.6 µM) was needed to reduce DNA damage and apoptosis while both concentrations of potassium iodide (0.5 and 1 µM) were protective ( < 0.05). A high concentration of copper (40 µM) increased apoptosis and DNA damage but this effect was no longer significant after induction of oxidative stress. Micronutrients supplementation can increase their content within the placenta and an optimal maternal micronutrient level is essential for placenta health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13030800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997475PMC
February 2021

Mitochondrial dysfunction in placental trophoblast cells experiencing gestational diabetes mellitus.

J Physiol 2021 02 15;599(4):1291-1305. Epub 2020 Nov 15.

School of Medical Science, Griffith Health, Griffith University, Gold Coast Campus, Southport, Queensland, Australia.

Key Points: Mitochondrial dysfunction is known to occur in diabetic phenotypes including type 1 and 2 diabetes mellitus. The incidence of gestational diabetes mellitus (GDM) is increasing and defined as the onset of a diabetic phenotype during pregnancy. The role of placental mitochondria in the aetiology of GDM remains unclear and is an emerging area of research. Differing mitochondrial morphologies within the placenta may influence the pathogenesis of the disorder. This study observed mitochondrial dysfunction in GDM placenta when assessing whole tissue. Upon further investigation into mitochondrial isolates from the cytotrophoblast and syncytiotrophoblast, mitochondrial dysfunction appears exaggerated in syncytiotrophoblast. Assessing mitochondrial populations individually enabled the determination of differences between cell lineages of the placenta and established varying levels of mitochondrial dysfunction in GDM, in some instances establishing significance in pathways previously inconclusive or confounded when assessing whole tissue. This research lays the foundation for future work into mitochondrial dysfunction in the placenta and the role it may play in the aetiology of GDM.

Abstract: Mitochondrial dysfunction has been associated with diabetic phenotypes, yet the involvement of placental mitochondria in gestational diabetes mellitus (GDM) remains inconclusive. This is in part complicated by the different mitochondrial subpopulations present in the two major trophoblast cell lineages of the placenta. To better elucidate the role of mitochondria in this pathology, this study examined key aspects of mitochondrial function in placentas from healthy pregnancies and those complicated by GDM in both whole tissue and isolated mitochondria. Mitochondrial content, citrate synthase activity, reactive oxygen species production and gene expression regulating metabolic, hormonal and antioxidant control was examined in placental tissue, before examining functional differences between mitochondrial isolates from cytotrophoblast (Cyto-Mito) and syncytiotrophoblast (Syncytio-Mito). Our study observed evidence of mitochondrial dysfunction across multiple pathways when assessing whole placental tissue from GDM pregnancies compared with healthy controls. Furthermore, by examining isolated mitochondria from the cytotrophoblast and syncytiotrophoblast cell lineages of the placenta we established that although both mitochondrial populations were dysfunctional, they were differentially impacted. These data highlight the need to consider changes in mitochondrial subpopulations at the feto-maternal interface when studying pregnancy pathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1113/JP280593DOI Listing
February 2021

Low serum selenium in pregnancy is associated with reduced T3 and increased risk of GDM.

J Endocrinol 2021 01;248(1):45-57

The School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.

Thyroid disorders are the most common endocrine disorders affecting women commencing pregnancy. Thyroid hormone metabolism is strongly influenced by selenium status; however, the relationship between serum selenium concentrations and thyroid hormones in euthyroid pregnant women is unknown. This study investigated the relationship between maternal selenium and thyroid hormone status during pregnancy by utilizing data from a retrospective, cross-sectional study (Maternal Outcomes and Nutrition Tool or MONT study) with cohorts from two tertiary care hospitals in South East Queensland, Australia. Pregnant women (n = 206) were recruited at 26-30 weeks gestation and serum selenium concentrations were assessed using inductively coupled plasma mass spectrometry. Thyroid function parameters were measured in serum samples from women with the lowest serum selenium concentrations (51.2 ± 1.2 µg/L), women with mean concentrations representative of the entire cohort (78.8 ± 0.4 µg/L) and women with optimal serum selenium concentrations (106.9 ± 2.3 µg/L). Women with low serum selenium concentrations demonstrated reduced fT3 levels (P < 0.05) and increased TPOAb (P < 0.01). Serum selenium was positively correlated with fT3 (P < 0.05) and negatively correlated with TPOAb (P < 0.001). Serum fT4 and thyroid-stimulating hormone (TSH) were not different between all groups, though the fT4/TSH ratio was increased in the low selenium cohort (P < 0.05). Incidence of pregnancy disorders, most notably gestational diabetes mellitus, was increased within the low serum selenium cohort (P < 0.01). These results suggest selenium status in pregnant women of South East Queensland may not be adequate, with possible implications for atypical thyroid function and undesirable pregnancy outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/JOE-20-0319DOI Listing
January 2021

Mitochondrial transformations in the aging human placenta.

Am J Physiol Endocrinol Metab 2020 12 21;319(6):E981-E994. Epub 2020 Sep 21.

School of Medical Science, Griffith University Gold Coast Campus, Southport, Queensland, Australia.

Mitochondria play a key role in homeostasis and are central to one of the leading hypotheses of aging, the free radical theory. Mitochondria function as a reticulated network, constantly adapting to the cellular environment through fusion (joining), biogenesis (formation of new mitochondria), and fission (separation). This adaptive response is particularly important in response to oxidative stress, cellular damage, and aging, when mitochondria are selectively removed through mitophagy, a mitochondrial equivalent of autophagy. During this complex process, mitochondria influence surrounding cell biology and organelles through the release of signaling molecules. Given that the human placenta is a unique organ having a transient and somewhat defined life span of ∼280 days, any adaption or dysfunction associated with mitochondrial physiology as a result of aging will have a dramatic impact on the health and function of both the placenta and the fetus. Additionally, a defective placenta during gestation, resulting in reduced fetal growth, has been shown to influence the development of chronic disease in later life. In this review we focus on the mitochondrial adaptions and transformations that accompany gestational length and share similarities with age-related diseases. In addition, we discuss the role of such changes in regulating placental function throughout gestation, the etiology of gestational complications, and the development of chronic diseases later in life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpendo.00354.2020DOI Listing
December 2020

Maternal High Linoleic Acid Alters Placental Fatty Acid Composition.

Nutrients 2020 Jul 23;12(8). Epub 2020 Jul 23.

Institute for Health and Sport, Victoria University, Melbourne, VIC 3000, Australia.

Fetal development is modulated by maternal nutrition during pregnancy. The dietary intake of linoleic acid (LA), an essential dietary n-6 polyunsaturated fatty acid (PUFA), has increased. We previously published that increased LA consumption during pregnancy does not alter offspring or placental weight but fetal plasma fatty acid composition; the developing fetus obtains their required PUFA from the maternal circulation. However, it is unknown if increased maternal linoleic acid alters placental fatty acid storage, metabolism, transport, and general placental function. Female Wistar-Kyoto rats were fed either a low LA diet (LLA; 1.44% of energy from LA) or high LA diet (HLA; 6.21% of energy from LA) for 10 weeks before pregnancy and during gestation. Rats were sacrificed at embryonic day 20 (E20, term = 22 days) and placentae collected. The labyrinth of placentae from one male and one female fetus from each litter were analyzed. High maternal LA consumption increased placental total n-6 and LA concentrations, and decreased total n-3 PUFA, alpha-linolenic acid (ALA), and docosahexaenoic acid (DHA). Fatty acid desaturase 1 (), angiopoietin-like 4 (), and diacylglycerol lipase beta () mRNA were downregulated in placentae from offspring from HLA dams. Maternal high LA downregulated the fatty acid transport protein 4 () and glucose transporter 1 () mRNA in placentae. IL-7 and IL-10 protein were decreased in placentae from offspring from HLA dams. In conclusion, a high maternal LA diet alters the placental fatty acid composition, inflammatory proteins, and expressions of nutrient transporters, which may program deleterious outcomes in offspring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12082183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468786PMC
July 2020

Effect of Iodine and Selenium on Proliferation, Viability, and Oxidative Stress in HTR-8/SVneo Placental Cells.

Biol Trace Elem Res 2021 Apr 5;199(4):1332-1344. Epub 2020 Jul 5.

School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Adelaide, SA, 5005, Australia.

Adequate maternal micronutrition is vital for placental formation, fetal growth, and development. Oxidative stress adversely affects placental development and function and an association between deficient placental development, oxidative stress, and micronutrient deficiency has been observed. Selenium and iodine are two essential micronutrients with antioxidant properties. Epidemiological studies have shown that poor micronutrient status in pregnant women is associated with a higher incidence of pregnancy complications. The aim of this study was to determine how selenium, iodine, and their combination impact oxidative stress in placental trophoblast cells. HTR8/SVneo extravillous trophoblasts were supplemented with a concentration range of organic and inorganic selenium, potassium iodide, or their combination for 24 h. Oxidative stress was then induced by treating cells with menadione or HO for 24 h. Cell viability and lipid peroxidation as the biomarker of oxidative stress were assessed at 48 h. Both menadione and HO reduced cell viability and increased lipid peroxidation (P < 0.05). Greater cell viability was found in selenium-supplemented cells when compared with vehicle treated cells (P < 0.05). Selenium and iodine supplementation separately or together were associated with lower lipid peroxidation compared with vehicle control (P < 0.05). Supplementation with the combination of selenium and iodine resulted in a greater reduction in lipid peroxidation compared with selenium or iodine alone (P < 0.05). Oxidative stress negatively impacts trophoblast cell survival and cellular integrity. Selenium and iodine protect placental trophoblasts against oxidative stress. Further research is warranted to investigate the molecular mechanisms by which selenium and iodine act in the human placenta.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-020-02277-7DOI Listing
April 2021

Effect of micronutrient supplements on low-risk pregnancies in high-income countries: a systematic quantitative literature review.

Public Health Nutr 2020 09 9;23(13):2434-2444. Epub 2020 Jun 9.

School of Medical Science, Menzies Health Institute Queensland, Griffith University, Southport, QLD 4015, Australia.

Objective: To assess the quantity and focus of recent empirical research regarding the effect of micronutrient supplementation on live birth outcomes in low-risk pregnancies from high-income countries.

Design: A systematic quantitative literature review.

Setting: Low-risk pregnancies in World Bank-classified high-income countries, 2019.

Results: Using carefully selected search criteria, a total of 2475 publications were identified, of which seventeen papers met the inclusion criteria for this review. Data contributing to nine of the studies were sourced from four cohorts; research originated from ten countries. These cohorts exhibited a large number of participants, stable data and a low probability of bias. The most recent empirical data offered by these studies was 2011; the most historical was 1980. In total, fifty-five categorical outcome/supplement combinations were examined; 67·3 % reported no evidence of micronutrient supplementation influencing selected outcomes.

Conclusions: A coordinated, cohesive and uniform empirical approach to future studies is required to determine what constitutes appropriate, effective and safe micronutrient supplementation in contemporary cohorts from high-income countries, and how this might influence pregnancy outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1368980020000725DOI Listing
September 2020

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

Biol Trace Elem Res 2021 Jan 1;199(1):26-40. Epub 2020 Apr 1.

School of Medical Science, Griffith University, Gold Coast Campus, Parklands Drive, Southport, QLD, 4215, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-020-02127-6DOI Listing
January 2021

Analysis of Selenoprotein Expression in Response to Dietary Selenium Deficiency During Pregnancy Indicates Tissue Specific Differential Expression in Mothers and Sex Specific Changes in the Fetus and Offspring.

Int J Mol Sci 2020 Mar 23;21(6). Epub 2020 Mar 23.

School of Medical Science, Menzies Health Institute Queensland, Griffith University Gold, Coast Campus, Southport, QLD 4215, Australia.

The human selenoproteome is comprised of ~25 genes, which incorporate selenium, in the form of selenocysteine, into their structure. Since it is well known that selenium is important to maternal health and foetal development during pregnancy, this study aimed at defining the impact of selenium deficiency on maternal, placental, foetal and offspring selenoprotein gene expression. Female mice were randomly allocated to control (>190 μg/kg) or low selenium (<50 μg/kg) diets four weeks prior to mating and throughout gestation. At embryonic day (E)18.5, pregnant mice were sacrificed followed by collection of maternal and foetal tissues. A subset of mice littered down, and offspring were monitored from postnatal day (PN) 8, weaned at PN24 and sacrificed at PN180, followed by tissue collection. Following RNA extraction, the expression of 14 selenoproteins was assessed with qPCR in liver, kidneys, muscle and placenta. Selenium deficiency downregulated expression ( < 0.05) of many selenoproteins in maternal tissues and the placenta. However, foetal selenoprotein expression was upregulated ( < 0.05) in all tissues, especially the kidneys. This was not reflected at PN180; however, a sexually dimorphic relationship in selenoprotein expression was observed in offspring. This study demonstrates the selenoproteome is sensitive to dietary selenium levels, which may be exacerbated by pregnancy. We concluded that transcriptional regulation of selenoproteins is complex and multifaceted, with expression exhibiting tissue-, age- and sex-specificities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21062210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139809PMC
March 2020

Influence of dietary intake and decision-making during pregnancy on birth outcomes.

Nutr Diet 2020 07 20;77(3):323-330. Epub 2020 Feb 20.

School of Medical Science, Menzies Health Institute Queensland, Griffith University Gold Coast Campus, Southport, Queensland, Australia.

Aim: This study aimed to examine dietary intake and decision-making in a cohort of pregnant South-East Queensland women to determine compliance with dietary guidelines and the relationships between dietary intake, decision-making and birth outcomes.

Methods: Pregnant women attending maternity services at participating hospitals reported food frequency and motivations using the Maternal Outcomes and Nutrition Tool, a novel digital instrument. Birth outcomes were sourced from hospital records. A cross-sectional cohort design was used to examine the data.

Results: Analysis demonstrated suboptimal intake of core food groups; meat and alternatives (median [IQR]) (2.6 [2.0-3.4] serves/day) and grains (3.1 [2.1-4.1]) fell below recommendations; fruit (3.8 [2.5-5.3]) and discretionary foods (3.1 [2.1-4.4]) exceeded them. Hypertensive disorders demonstrated a negative linear relationship with vegetable intake (P = .017). Cultural diversity was significantly associated with decreased birthweight (P = .022) but increased intake of meat and alternatives (3.1 vs 2.6, P < .001) compared to Caucasian women; median intake of meat and alternatives was lower in women who reported smoking in the examined time frame. Smokers were less likely to declare health motives for food selection than non-smokers; smoking and health were inversely associated with increasing maternal age. Food choice was primarily sensory-driven.

Conclusions: This cohort demonstrated poor adherence to dietary guidelines. Culturally and linguistically diverse women and smokers exhibit dietary behaviours which may contribute to suboptimal birth outcomes; targeted nutrition counselling may improve outcomes in these women. These findings highlight the need for transdisciplinary maternity care and provide a foundation for further research aimed at optimising nutrition-related birth outcomes in at-risk groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1747-0080.12610DOI Listing
July 2020

Maternal Selenium Deficiency in Mice Alters Offspring Glucose Metabolism and Thyroid Status in a Sexually Dimorphic Manner.

Nutrients 2020 Jan 20;12(1). Epub 2020 Jan 20.

School of Medical Science, Menzies Health Institute Queensland, Griffith University Gold, Coast Campus, Southport, QLD 4215, Australia.

Selenium is an essential micronutrient commonly deficient in human populations. Selenium deficiency increases the risks of pregnancy complications; however, the long-term impact of selenium deficiency on offspring disease remains unclear. This study investigates the effects of selenium deficiency during pregnancy on offspring metabolic function. Female C57BL/6 mice were allocated to control (>190 μg selenium/kg, = 8) or low selenium (<50 μg selenium/kg, = 8) diets prior to mating and throughout gestation. At postnatal day (PN) 170, mice underwent an intraperitoneal glucose tolerance test and were culled at PN180 for biochemical analysis. Mice exposed to selenium deficiency in utero had reduced fasting blood glucose but increased postprandial blood glucose concentrations. Male offspring from selenium-deficient litters had increased plasma insulin levels in conjunction with reduced plasma thyroxine (tetraiodothyronine or T4) concentrations. Conversely, females exposed to selenium deficiency in utero exhibited increased plasma thyroxine levels with no change in plasma insulin. This study demonstrates the importance of adequate selenium intake around pregnancy for offspring metabolic health. Given the increasing prevalence of metabolic disease, this study highlights the need for appropriate micronutrient intake during pregnancy to ensure a healthy start to life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12010267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020085PMC
January 2020

Proteomic Analysis of Placental Mitochondria Following Trophoblast Differentiation.

Front Physiol 2019 20;10:1536. Epub 2019 Dec 20.

School of Medical Science, Griffith Health, Griffith University, Southport, QLD, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2019.01536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933824PMC
December 2019

Use of micronutrient supplements in pregnant women of south-east Queensland.

Aust N Z J Obstet Gynaecol 2020 08 5;60(4):561-567. Epub 2020 Jan 5.

School of Medical Science, Menzies Health Institute Queensland, Griffith University Gold Coast Campus, Southport, Queensland, Australia.

Background: Multiple micronutrient supplement use in the Australian pregnant population is rising, despite little evidence of benefit in low-risk women. While some supplement recommendations are grounded in high-quality evidence, others warrant further investigation. This highlights a research gap regarding appropriate use of supplements during pregnancy in the Australian population.

Aims: To describe micronutrient supplement use during pregnancy in the context of current evidence and national recommendations in a population of south-east Queensland women.

Material And Methods: A cross-sectional observational design was used to examine data gathered from pregnant women aged 16-44 years residing in south-east Queensland, Australia. Women were recruited to the study between 23 May 2016 and 30 September 2017.

Results: Pregnancy multivitamin use was declared by 42% of the cohort, with 26.8% declaring multivitamins in combination with individual micronutrients and 9.8% declaring specific micronutrient supplement use. Nulliparous women were more likely to declare use of supplements than their multiparous peers (adjusted odds ratio (aOR) 1.938, 95% CI 1.053-3.571, P = 0.034); smoking (aOR 2.717, 95% CI 1.011-7.302, P = 0.047) and low socio-economic status were associated with no supplement use (aOR 2.451, 95% CI 1.010-5.949, P = 0.048).

Conclusions: Current recommendations regarding micronutrient supplements throughout pregnancy are based on varying degrees of evidence, resulting in supplement advice of poor cohesion and consistency. Adherence to micronutrient supplement recommendations in the peri-conception period in this population was poor; second and third trimester supplement use was high. Contemporary empirical research is required to determine what constitutes appropriate supplementation in high-income regions and the populations they will benefit most.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajo.13109DOI Listing
August 2020

Role of omega-6 and omega-3 fatty acids in fetal programming.

Clin Exp Pharmacol Physiol 2020 05 28;47(5):907-915. Epub 2020 Jan 28.

Institute for Health and Sport, Victoria University, Melbourne, Vic., Australia.

Maternal nutrition plays a critical role in fetal development and can influence adult onset of disease. Linoleic acid (LA) and alpha-linolenic acid (ALA) are major omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA), respectively, that are essential in our diet. LA and ALA are critical for the development of the fetal neurological and immune systems. However, in recent years, the consumption of n-6 PUFA has increased gradually worldwide, and elevated n-6 PUFA consumption may be harmful to human health. Consumption of diets with high levels of n-6 PUFA before or during pregnancy may have detrimental effects on fetal development and may influence overall health of offspring in adulthood. This review discusses the role of n-6 PUFA in fetal programming, the importance of a balance between n-6 and n-3 PUFAs in the maternal diet, and the need of further animal models and human studies that critically evaluate both n-6 and n-3 PUFA contents in diets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1440-1681.13244DOI Listing
May 2020

Elemental metabolomics in human cord blood: Method validation and trace element quantification.

J Trace Elem Med Biol 2020 May 24;59:126419. Epub 2019 Oct 24.

School of Medical Science, Griffith University, Gold Coast Campus, Southport, 9726, Queensland, Australia. Electronic address:

Background: Trace elements are an essential requirement for human health and development and changes in trace element status have been associated with pregnancy complications such as gestational diabetes mellitus (GDM), pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth. Elemental metabolomics, which involves the simultaneous quantification and characterisation of multiple elements, could provide important insights into these gestational disorders.

Methods: This study used an Agilent 7900 inductively coupled plasma mass spectrometer (ICP-MS) to simultaneously measure 68 elements, in 166 placental cord blood samples collected from women with various pregnancy complications (control, hypertensive, PE, GDM, FGR, pre-term, and post-term birth).

Results: There were single element differences across gestational outcomes for elements Mg, P, Cr, Ni, Sr, Mo, I, Au, Pb, and U. Hypertensive and post-term pregnancies were significantly higher in Ni concentrations when compared to controls (control = 2.74 μg/L, hypertensive = 6.72 μg/L, post-term = 7.93 μg/L, p < 0.05), iodine concentration was significantly higher in post-term pregnancies (p < 0.05), and Pb concentrations were the lowest in pre-term pregnancies (pre-term = 2.79 μg/L, control = 4.68 μg/L, PE = 5.32 μg/L, GDM = 8.27 μg/L, p < 0.01). Further analysis was conducted using receiver operating characteristic (ROC) curves for differentiating pregnancy groups. The ratio of Sn/Pb showed the best diagnostic power in discriminating between control and pre-term birth with area under the curve (AUC) 0.86. When comparing control and post-term birth, Mg/Cr (AUC = 0.84), and Cr (AUC = 0.83) had the best diagnostic powers. In pre-term and post-term comparisons Ba was the best single element (81.5%), and P/Cu provided the best ratio (91.7%).

Conclusions: This study has shown that analysis of multiple elements can enable differentiation between fetal cord blood samples from control, hypertensive, PE, GDM, FGR, pre and post-term pregnancies. This data highlights the power of elemental metabolomics and provides a basis for future gestational studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtemb.2019.126419DOI Listing
May 2020

Essential Mineral Intake During Pregnancy and Its Association With Maternal Health and Birth Outcomes in South East Queensland, Australia.

Nutr Metab Insights 2019 29;12:1178638819879444. Epub 2019 Sep 29.

School of Medical Science, Menzies Health Institute Queensland, Griffith University, Southport, QLD, Australia.

Micronutrient supplements are often recommended during pregnancy, yet their role and necessity remain poorly understood in the Australian population. This study aimed to determine the essential mineral intake of a population of pregnant women in South East Queensland and investigate the effects of supplements on their micronutrient status and birth outcomes. Women completing the Oral Glucose Tolerance Test at two South East Queensland hospitals between 180 and 210 days gestation provided fasting blood samples and dietary data using the Maternal Outcomes and Nutrition Tool (n = 127). Birth outcomes were sourced from medical records. Serum elemental profiles were determined by inductively coupled plasma mass spectrometry (ICP-MS) analysis. Intake of 8 essential minerals was compared with Australian dietary recommendations; matched serum mineral levels were compared with the current Queensland pregnancy reference ranges. Data were examined using cross-sectional cohort design and independent sample -tests. Supplement use had no significant influence on serum values of trace elements or the incidence of hypertensive disorders, gestational diabetes, preterm birth or infant birthweight. Dietary selenium, zinc and iodine were significantly higher in women birthing beyond 41 completed weeks; selenium ( = .026) and zinc ( = .034) both made unique contributions to the regression models when controlling for confounders. Women exhibited adequate to excessive serum micronutrient levels compared with pregnancy reference ranges, a finding consistent with dietary intake calculations. Data suggest that excessive essential mineral intake contributed to prolonged pregnancy in this cohort, supporting previous studies in this population. Further research is required to determine individual needs and eliminate the potential for harm before recommending pregnancy supplements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1178638819879444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769211PMC
September 2019

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

J Physiol 2019 12 30;597(23):5597-5617. Epub 2019 Oct 30.

School of Medical Science, Menzies Health Institute Queensland, Griffith University Gold Coast Campus, Southport, QLD, Australia.

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 , n = 8) or low selenium (<50 µg kg , 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1113/JP278473DOI Listing
December 2019

Placental mitochondria and reactive oxygen species in the physiology and pathophysiology of pregnancy.

Clin Exp Pharmacol Physiol 2020 01 15;47(1):176-184. Epub 2019 Sep 15.

School of Medical Science, Griffith University, Gold Coast Campus, Southport, Queensland, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1440-1681.13172DOI Listing
January 2020

Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility.

Nutrients 2019 Jul 16;11(7). Epub 2019 Jul 16.

Robinson Research Institute, University of Adelaide, 5005 North Adelaide, South Australia, Australia.

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women ( = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks' gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99-1.44)) or who had lower selenium concentrations (1.19 (1.01-1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06-2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11071609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683068PMC
July 2019

Elevated maternal linoleic acid reduces circulating leptin concentrations, cholesterol levels and male fetal survival in a rat model.

J Physiol 2019 07 2;597(13):3349-3361. Epub 2019 Jun 2.

School of Environment and Science, Griffith University, Nathan, QLD, Australia.

Key Points: Linoleic acid consumption is increasing in Western populations. We investigated whether elevated linoleic acid in pregnancy was deleterious to mothers or offspring. Maternal and fetal body and organ weights were not affected by elevated linoleic acid consumption. Maternal lipids and leptin were altered following elevated linoleic acid consumption. Male offspring numbers were reduced following elevated linoleic acid consumption.

Abstract: Dietary intakes of linoleic acid (LA) have increased dramatically in Western populations, including in women of reproductive age. Pro-inflammatory effects of LA may have detrimental effects on maternal and offspring outcomes. We aimed to investigate whether consumption of a maternal diet with elevated LA altered maternal inflammatory or metabolic markers during pregnancy, fetal growth and/or the sex ratio of the offspring. Female Wistar Kyoto rats consumed a diet high in LA (HLA) (6.21% of energy) or a diet low in LA (LLA) (1.44% of energy) for 10 weeks prior to mating and during pregnancy. Pregnant rats were killed at embryonic day 20 (E20). There were no differences in maternal or fetal body weights or organ weights in the HLA group compared to the LLA group. There was no difference in maternal circulating cytokine concentrations between dietary groups. In the maternal liver, IL-1α concentrations were significantly lower, and TNF-α and IL-7 significantly higher in the HLA group. Total plasma cholesterol, LDL-cholesterol, HDL cholesterol and the total:HDL cholesterol ratio were lower in dams fed the HLA diet. mRNA expression of sterol regulatory element binding transcription factor 1 (SREBF-1) and leptin in maternal adipose tissue was lower in the HLA group, as were circulating leptin concentrations. The proportion of male fetuses was lower and circulating prostaglandin E metabolite concentrations were increased in the HLA group. In conclusion, consumption of a maternal diet high in linoleic acid alters cholesterol metabolism and prostaglandin E metabolite concentrations, which may contribute to the reduced proportion of male offspring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1113/JP277583DOI Listing
July 2019

Maternal corticosterone in the mouse alters oxidative stress markers, antioxidant function and mitochondrial content in placentas of female fetuses.

J Physiol 2019 06 20;597(12):3053-3067. Epub 2019 May 20.

School of Medical Science, Griffith University, Gold Coast Campus, Southport, Queensland, Australia.

Key Points: Maternal exposure to the stress hormone corticosterone is known to programme a range of sex specific disease outcomes in offspring. Sex differences in placental adaptations are thought to mediate these processes. Placental oxidative stress is implicated in a range of pregnancy disorders but the role of placental oxidative stress in sex specific disease outcomes following prenatal corticosterone exposure is unknown. This study demonstrates that maternal corticosterone reduced placental hydrogen peroxide and 8-hydroxy-2'-deoxyguanosine concentrations but increased protein carbonyl content and advanced glycation end product concentrations in placentas of female fetuses but not male fetuses. These results highlight that placentas of female fetuses respond differently to maternal corticosterone exposure, with oxidative stress a major finding in placentas of female fetuses.

Abstract: Maternal exposure to glucocorticoids during pregnancy increases offspring risk of developing a range of sex specific disease phenotypes. These sex specific disease outcomes are thought to be in part mediated by different placental adaptations in males and females. The placenta is a highly metabolic organ which is vulnerable to the effects of oxidative stress. In other tissues, males and females have been shown to respond differently to the pro-oxidant effects of glucocorticoids. This study therefore used a well characterized animal model of maternal corticosterone exposure to investigate sex specific alterations in reactive oxygen species production, antioxidant concentrations and mitochondrial properties that might contribute to sex differences in placental outcomes. C57BL/6 mice were implanted with osmotic minipumps containing corticosterone (33 μg kg  h ) at embryonic day (E) 12.5 and placentas collected at E14.5 for analysis. Corticosterone exposure reduced placental hydrogen peroxide (H O ) and 8-hydroxy-2'-deoxyguanosine concentrations but increased protein carbonyl content and advanced glycation end product concentrations in placentas of female fetuses but not male fetuses. This dysregulation of different markers of oxidative stress may be due to increased placental activity of thioredoxin reductase in female but not male fetuses. Corticosterone reduced placental mitochondrial content but increased protein expression of the autophagosome cargo protein p62. This study demonstrates that placentas of female fetuses respond differently to maternal corticosterone exposure and highlights an important role of reactive oxygen species, mitochondrial adaptations and antioxidant responses in glucocorticoid induced programmed disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1113/JP277815DOI Listing
June 2019

Linoleic Acid Increases Prostaglandin E2 Release and Reduces Mitochondrial Respiration and Cell Viability in Human Trophoblast-Like Cells.

Cell Physiol Biochem 2019 18;52(1):94-108. Epub 2019 Feb 18.

Institute for Health and Sport, Victoria University, Melbourne, Australia.

Background/aims: The omega 6 fatty acid (FA) linoleic acid (LA) is required for embryonic development; however, omega 6 FAs can alter cellular metabolism via inflammation or modulation of mitochondrial function. Fetal LA is obtained from the maternal diet, and FAs are transported to the fetus via placental FA transporters (FATPs) and binding proteins (FABPs), but specific proteins responsible for LA transport in placental trophoblasts are unknown. Dietary LA consumption is increasing, but the effect of elevated LA on trophoblast function is not clear.

Methods: Swan71 trophoblasts were exposed to physiological and supraphysiological concentrations of LA for 24 hours. Quantification of mRNA was determined using real time PCR, and protein concentration was determined by Western blot analysis. Cell viability, citrate synthase activity and mitochondrial respiration were determined.

Results: Exposure to 300 and 500 μM LA increased FATP1 and FATP4 mRNA expression. 500 μM LA increased FATP1 and FATP4 protein expression. Exposure to 500 μM increased FABP5 mRNA expression, while exposure to 100 to 500 μM LA decreased FABP3 mRNA expression. 300 and 500 μM LA decreased FABP3 protein expression. Cell viability was decreased by exposure to LA (100 to 1000 μM). Citrate synthase activity and routine mitochondrial respiration were significantly decreased by exposure to 300 and 500 μM LA, and maximal respiration and spare respiratory capacity were decreased by exposure to 100 to 500 μM LA. 300 and 500 μM LA increased reactive oxygen species generation in human trophoblasts. Moreover, exposure to 300 and 500 μM LA decreased IL-6 secretion. Exposure to 500 μM LA increased IL-8, NF-κB and PPAR-γ mRNA expression, but decreased NF-κB protein expression. 300 μM LA decreased IL-8 protein expression. Further, exposure to 100 to 500 μM LA increased prostaglandin E2 and leukotriene B₄ release.

Conclusion: Exposure to LA decreases cell viability, alters mRNA expression of FA transport related proteins, mitochondrial respiration and function, and inflammatory responses in trophoblasts. These findings may have implications on placental function when women consume high levels of LA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.33594/000000007DOI Listing
March 2019

Elemental Metabolomics and Pregnancy Outcomes.

Nutrients 2019 Jan 2;11(1). Epub 2019 Jan 2.

School of Medical Science, Menzies Health Institute Queensland, Griffith University, Southport 9726, Queensland, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11010073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356574PMC
January 2019

Placental mitochondrial adaptations in preeclampsia associated with progression to term delivery.

Cell Death Dis 2018 11 19;9(12):1150. Epub 2018 Nov 19.

School of Medical Science, Griffith University, Gold Coast Campus, Southport, QLD, Australia.

Preeclampsia is a devastating pregnancy disorder. Severity varies widely, and while severe preeclampsia often requires pre-term delivery, women with mild preeclampsia may reach term with minor interventions. The mechanisms that mediate disease severity are poorly understood, but may include adaptive processes by the placenta. We aimed to establish whether in pregnancies that reached term and those that delivered pre-term, the placental response to preeclampsia was intrinsically different, and explore potential adaptive mechanisms. Hydrogen peroxide production and antioxidant activity were increased in term preeclamptic placentae, whereas pre-term preeclamptic placentae had reduced hydrogen peroxide production and reduced function of the antioxidant system superoxide dismutase compared to control placentae. Markers of mitochondrial fission/fusion, apoptosis and the expression level of mitochondrial complexes were differentially disrupted in term compared to pre-term preeclamptic placentae. Mitochondrial respiration and content were increased in term preeclamptic placentae, but mitochondria had a lower respiratory reserve capacity. Mitochondrial respiration and hydrogen peroxide production were increased in healthy term placentae after in vitro hypoxia/reoxygenation. Placentae from preeclamptic pregnancies that reached term showed multiple adaptions that were not present in pre-term preeclamptic placentae. Increased antioxidant activity, and expression of markers of mitochondrial fusion and apoptotic suppression, may relate to salvaging damaged mitochondria. Increased mitochondrial respiration may allow ongoing tissue function even with reduced respiratory efficiency in term preeclamptic pregnancies. Response after in vitro hypoxia/reoxygenation suggests that disruption of oxygen supply is key to placental mitochondrial adaptations. Reactive oxygen species signalling in term preeclamptic placentae may be at a level to trigger compensatory antioxidant and mitochondrial responses, allowing tissue level maintenance of function when there is organelle level dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-018-1190-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242930PMC
November 2018