ORCID Profile
0000-0002-6326-4797
Current Organisations
Macquarie University
,
University of South Australia
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Publisher: Wiley
Date: 06-2023
DOI: 10.14814/PHY2.15749
Abstract: Babies born growth restricted are at an increased risk of both poor short‐and long‐term outcomes. Current interventions to improve fetal growth are ineffective and do not lower the lifetime risk of poor health status. Maternal resveratrol (RSV) treatment increases uterine artery blood flow, fetal oxygenation, and fetal weight. However, studies suggest that diets high in polyphenols such as RSV may impair fetal hemodynamics. We aimed to characterize the effect of RSV on fetal hemodynamics to further assess its safety as an intervention strategy. Pregnant ewes underwent magnetic resonance imaging (MRI) scans to measure blood flow and oxygenation within the fetal circulation using phase contrast‐MRI and T 2 oximetry. Blood flow and oxygenation measures were performed in a basal state and then repeated while the fetus was exposed to RSV. Fetal blood pressure and heart rate were not different between states. RSV did not impact fetal oxygen delivery (DO 2 ) or consumption (VO 2 ). Blood flow and oxygen delivery throughout the major vessels of the fetal circulation were not different between basal and RSV states. As such, acute exposure of the fetus to RSV does not directly impact fetal hemodynamics. This strengthens the rationale for the use of RSV as an intervention strategy against fetal growth restriction.
Publisher: Elsevier BV
Date: 09-2023
Publisher: American Physiological Society
Date: 2008
DOI: 10.1152/AJPCELL.00155.2007
Abstract: We compared the effects of 50 mM P i on caffeine-induced Ca 2+ release in mechanically skinned fast-twitch (FT) and slow-twitch (ST) skeletal muscle fibers of the rat. The time integral (area) of the caffeine response was reduced by ∼57% (FT) and ∼27% (ST) after 30 s of exposure to 50 mM P i in either the presence or absence of creatine phosphate (to buffer ADP). Differences in the sarcoplasmic reticulum (SR) Ca 2+ content between FT and ST fibers [∼40% vs. 100% SR Ca 2+ content (pCa 6.7), respectively] did not contribute to the different effects of P i observed underloading the SR of ST fibers so that the SR Ca 2+ content approximated that of FT fibers resulted in an even smaller (∼21%), but not significant, reduction in caffeine-induced Ca 2+ release by P i . These observed differences between FT and ST fibers could arise from fiber-type differences in the ability of the SR to accumulate Ca 2+ -P i precipitate. To test this, fibers were Ca 2+ loaded in the presence of 50 mM P i . In FT fibers, the maximum SR Ca 2+ content (pCa 6.7) was subsequently increased by up to 13 times of that achieved when loading for 2 min in the absence of P i . In ST fibers, the SR Ca 2+ content was only doubled. These data show that Ca 2+ release in ST fibers was less affected by P i than FT fibers, and this may be due to a reduced capacity of ST SR to accumulate Ca 2+ -P i precipitate. This may account, in part, for the fatigue-resistant nature of ST fibers.
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.LFS.2022.120521
Abstract: Maternal undernutrition during pregnancy disrupts both fetal growth and development with perturbations to certain physiological processes within the maternal-fetal-placental unit, including metabolic function. However, it is unknown if hypoglycemia during pregnancy alters maternal-fetal-placental drug metabolism as mediated by cytochrome P450 (CYP) enzymes. Despite this, hypoglycemia reduces CYP enzyme activity in non-pregnant animals. We therefore hypothesised that in a sheep model of hypoglycemia induced by late gestation undernutrition (LGUN), maternal-fetal-placental CYP activity would be reduced, and that fetal glucose infusion (LGUN+G) would rescue reduced CYP activity. At 115d gestation (term, 150d), ewes were allocated to control (100% metabolic energy requirement (MER) n = 11), LGUN (50% MER n = 7) or LGUN+G (50% MER + fetal glucose infusion n = 6) and maintained on their diets until post-mortem. Maternal-fetal-placental CYP activity assays were performed at 131-133d gestation. Microsomes were isolated from placenta and fetal liver collected at 139-142d gestation and incubated with CYP-specific probe drugs. Metabolite concentrations were measured using Liquid Chromatography - tandem mass spectrometry (LC-MS/MS). CYP2C19 and CYP3A were undetectable in placenta or fetal liver, and CYP1A2 was undetectable in the fetal liver. Placental-specific CYP1A2 and CYP2D6 activity and hepatic-specific CYP2D6 activity were unaffected by LGUN. Maternal-fetal-placental CYP1A2 activity was reduced in response to LGUN in the maternal compartment only. Reduced maternal-fetal-placental CYP1A2 activity, but not placental-specific CYP1A2 activity, may lead to the developing fetus being exposed to increased concentrations of CYP1A2-specific substrates and suggests further consideration of drug dosing is required in instances of late gestation maternal undernutrition.
Publisher: Elsevier BV
Date: 07-2023
Publisher: S. Karger AG
Date: 2022
DOI: 10.1159/000526972
Abstract: b i Introduction: /i /b Newborns exposed to sildenafil citrate (SC) in utero have increased rates of persistent pulmonary hypertension. The mechanism behind this has not yet been fully elucidated. We aimed to utilize a combination of clinically relevant MRI techniques to comprehensively characterize the haemodynamics of the fetal sheep whilst under the influence of SC. We hypothesized that these MRI techniques would detect SC-induced increases in pulmonary blood flow and oxygen delivery prior to birth. b i Methods: /i /b At 116–117 days gestational age (term, 150 days), pregnant Merino ewes ( i n /i = 9) underwent fetal catheterization surgery. MRI scans were performed during a basal state and then repeated during a constant umbilical vein infusion of SC to measure blood flow and oxygenation within the major vessels of the fetal circulation using phase-contrast-MRI and T sub /sub oximetry. b i Results: /i /b Right and left ventricular cardiac outputs were not different between states. Pulmonary blood flow increased during the SC state resulting in elevated pulmonary oxygen delivery. Right to left heart shunting through the foramen ovale was reduced without reducing cerebral oxygen delivery. b i Conclusion: /i /b SC induces alterations to pulmonary haemodynamics i in utero /i a characteristic that if maintained may underlie or act as a precursor towards the elevated rates of poor pulmonary outcomes after birth. These MRI techniques are the first to comprehensively characterize sildenafil’s direct impact on the pulmonary vasculature and its indirect detriment to the flow of oxygen-rich blood through the foramen ovale.
Publisher: Wiley
Date: 04-2021
DOI: 10.1113/JP280803
Abstract: The margin of human viability has extended to the extremes of gestational age ( weeks) when the lungs are immature and ventilator‐induced lung injury is common. Artificial placenta technology aims to extend gestation ex utero in order to allow the lungs additional time to develop prior to entering an air‐breathing environment. We compared the haemodynamics and cerebral oxygenation of piglets in the immediate period post‐oxygenator (OXY) transition against both paired in utero measures and uniquely against piglets transitioned onto mechanical ventilation (VENT). Post‐transition, OXY piglets became hypotensive with reduced carotid blood flow in comparison with both paired in utero measures and VENT piglets. The addition of a pump to the oxygenator circuit may be required to ensure haemodynamic stability in the immediate post‐transition period. Gestational age at birth is a major predictor of wellbeing the lower the gestational age, the greater the risk of mortality and morbidity. At the margins of human viability ( weeks gestation) immature lungs combined with the need for early ventilatory support means lung injury and respiratory morbidity is common. The abrupt haemodynamic changes consequent on birth may also contribute to preterm‐associated brain injury, including intraventricular haemorrhage. Artificial placenta technology aims to support oxygenation, haemodynamic stability and ongoing fetal development ex utero until mature enough to safely transition to a true ex utero environment. We aimed to characterize the impact of birth transition onto either an oxygenator circuit or positive pressure ventilation on haemodynamic and cerebral oxygenation of the neonatal piglet. At 112 days gestation (term = 115 days), fetal pigs underwent instrumentation surgery and transitioned onto either an oxygenator (OXY, n = 5) or ventilatory support (VENT, n = 8). Blood pressure (BP), carotid blood flow and cerebral oxygenation in VENT piglets rose from in utero levels to be significantly higher than OXY piglets post‐transition. OXY piglet BP, carotid blood flow and carotid oxygen delivery (DO 2 ) decreased from in utero levels post‐transition however, cerebral regional oxygen saturation (rSO 2 ) was maintained at fetal‐like levels. OXY piglets became hypoxaemic and retained CO 2 . Whether OXY piglets are able to maintain cerebral rSO 2 under these conditions for a prolonged period is yet to be determined. Improvements to OXY piglet oxygenation may lie in maintaining piglet BP at in utero levels and enhancing oxygenator circuit flow.
Publisher: Wiley
Date: 07-2020
DOI: 10.1113/JP279631
Publisher: Cambridge University Press (CUP)
Date: 07-01-2021
DOI: 10.1017/S204017442000135X
Abstract: Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ , surfactant proteins ( SFTP-A, -B, -C , and -D ), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1 . Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B . However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.
Publisher: Oxford University Press (OUP)
Date: 25-06-2019
DOI: 10.1093/AF/VFZ019
Publisher: Wiley
Date: 02-2020
DOI: 10.14814/PHY2.14365
Publisher: Wiley
Date: 22-09-2021
DOI: 10.1113/JP281292
Abstract: Restriction of fetal substrate supply has an adverse effect on surfactant maturation in the lung and thus affects the transition from in utero placental oxygenation to pulmonary ventilation ex utero . The effects on surfactant maturation are mediated by alteration in mechanisms regulating surfactant protein and phospholipid synthesis. This study aimed to determine the effects of late gestation maternal undernutrition (LGUN) and LGUN plus fetal glucose infusion (LGUN+G) compared to Control on surfactant maturation and lung development, and the relationship with pulmonary blood flow and oxygen delivery ( ) measured by magnetic resonance imaging (MRI) with molecules that regulate lung development. LGUN from 115 to 140 days’ gestation significantly decreased fetal body weight, which was normalized by glucose infusion. LGUN and LGUN+G resulted in decreased fetal plasma glucose concentration, with no change in fetal arterial compared to control. There was no effect of LGUN and LGUN+G on the mRNA expression of surfactant proteins ( SFTP ) and genes regulating surfactant maturation in the fetal lung. However, blood flow in the main pulmonary artery was significantly increased in LGUN, despite no change in blood flow in the left or right pulmonary artery and to the fetal lung. There was a negative relationship between left pulmonary artery flow and to the left lung with SFTP‐B and GLUT1 mRNA expression, while their relationship with VEGFR2 was positive. These results suggest that increased pulmonary blood flow measured by MRI may have an adverse effect on surfactant maturation during fetal lung development. image Maternal undernutrition during gestation alters fetal lung development by impacting surfactant maturation. However, the direction of change remains controversial. We examined the effects of maternal late gestation maternal undernutrition (LGUN) on maternal and fetal outcomes, signalling pathways involved in fetal lung development, pulmonary haemodynamics and oxygen delivery in sheep using a combination of molecular and magnetic resonance imaging (MRI) techniques. LGUN decreased fetal plasma glucose concentration without affecting arterial . Surfactant maturation was not affected however, main pulmonary artery blood flow was significantly increased in the LGUN fetuses. This is the first study to explore the relationship between in utero MRI measures of pulmonary haemodynamics and lung development. Across all treatment groups, left pulmonary artery blood flow and oxygen delivery were negatively correlated with surfactant protein B mRNA and protein expression in late gestation.
Publisher: Wiley
Date: 03-2021
DOI: 10.14814/PHY2.14742
Publisher: American Physiological Society
Date: 02-2015
DOI: 10.1152/AJPREGU.00036.2014
Abstract: In the fetus, there is a redistribution of cardiac output in response to acute hypoxemia, to maintain perfusion of key organs, including the brain, heart, and adrenal glands. There may be a similar redistribution of cardiac output in the chronically hypoxemic, intrauterine growth-restricted fetus. Surgical removal of uterine caruncles in nonpregnant ewe results in the restriction of placental growth (PR) and intrauterine growth. Vascular catheters were implanted in seven control and six PR fetal sheep, and blood flow to organs was determined using microspheres. Placental and fetal weight was significantly reduced in the PR group. Despite an increase in the relative brain weight in the PR group, there was no difference in blood flow to the brain between the groups, although PR fetuses had higher blood flow to the temporal lobe. Adrenal blood flow was significantly higher in PR fetuses, and there was a direct relationship between mean gestational Pa O 2 and blood flow to the adrenal gland. There was no change in blood flow, but a decrease in oxygen and glucose delivery to the heart in the PR fetuses. In another group, there was a decrease in femoral artery blood flow in the PR compared with the Control group, and this may support blood flow changes to the adrenal and temporal lobe. In contrast to the response to acute hypoxemia, these data show that there is a redistribution of blood flow to the adrenals and temporal lobe, but not the heart or whole brain, in chronically hypoxemic PR fetuses in late gestation.
Publisher: Wiley
Date: 23-12-2020
Abstract: The primary metabolic pathway required to produce ATP differs as a result of tissue type, developmental stage and substrate availability. We utilized molecular and histological techniques to define the metabolic status in foetal and adult, adipose and skeletal muscle tissues. Redox ratios of these tissues were also determined optically by two-photon microscopy. Adult perirenal adipose tissue had a higher optical redox ratio than fetal perirenal adipose tissue, which aligned with glycolysis being used for ATP production whereas adult skeletal muscle had a lower optical redox ratio than fetal skeletal muscle, which aligned with oxygen demanding oxidative phosphorylation activity being utilized for ATP production. We have compared traditional molecular and microscopy techniques of metabolic tissue characterization with optical redox ratios to provide a more comprehensive report on the dynamics of tissue metabolism.
Publisher: Routledge
Date: 17-04-2018
Publisher: Elsevier BV
Date: 11-2021
Publisher: Informa UK Limited
Date: 19-12-2013
Publisher: Emerald
Date: 07-01-2014
DOI: 10.1108/IJEM-06-2012-0076
Abstract: – Many universities are in the process of changing their learning management systems to Moodle yet there is limited empirical research available on the impact of this change. The purpose of this paper is to explore the results of an initial pilot, which was conducted as the first stage of implementing Moodle at an Australian university. – The pilot study involved an online survey and a focus group with unit convenors teaching Open University Australia (OUA) units in Moodle. – The aim was to essentially test Moodle and eliminate any technological issues prior to the university-wide roll-out the following year. It was envisaged that this pilot would contribute to building capability and knowledge amongst staff members however, it was unanticipated that this would be jeopardised by a wider and ongoing issue in higher education namely, the casualisation of the academic workforce. The paper maps the accumulated knowledge of these unit convenors and how this knowledge is “walking out the door”. – The paper argues that an environment of insecure employment is a barrier to change management.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.PLACENTA.2019.06.380
Abstract: Maternal asthma increases the risk of adverse pregnancy outcomes and may affect fetal growth and placental function by differential effects on the expression of glucocorticoid receptor (GR) isoforms, leading to altered glucocorticoid signalling. Our aim was to examine the effect of maternal asthma on placental GR profiles using a pregnant sheep model of asthma. Nine known GR isoforms were detected. There was a significant increase in the expression of placental GR isoforms that are known to have low trans-activational activity in other species including GR A, GR P and GRγ which may result in a pro-inflammatory environment in the presence of allergic asthma.
Publisher: Wiley
Date: 02-06-2020
DOI: 10.1113/JP279054
Publisher: Wiley
Date: 23-08-2020
DOI: 10.1113/JP280019
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 16-09-2021
Abstract: Intrauterine growth restriction (IUGR) is a result of limited substrate supply to the developing fetus in utero, and can be caused by either placental, genetic or environmental factors. Babies born IUGR can have poor long‐term health outcomes, including being at higher risk of developing cardiovascular disease. Limited substrate supply in the IUGR fetus not only changes the structure of the heart but may also affect metabolism and function of the developing heart. We have utilised two imaging modalities, two‐photon microscopy and phase‐contrast MRI (PC‐MRI), to assess alterations in cardiac metabolism and function using a sheep model of IUGR. Two‐photon imaging revealed that the left ventricle of IUGR fetuses (at 140–141 d GA) had a reduced optical redox ratio, suggesting a reliance on glycolysis for ATP production. Concurrently, the use of PC‐MRI to measure foetal left ventricular cardiac output (LVCO) revealed a positive correlation between LVCO and redox ratio in IUGR, but not control fetuses. These data suggest that altered heart metabolism in IUGR fetuses is indicative of reduced cardiac output, which may contribute to poor cardiac outcomes in adulthood.
Publisher: Elsevier BV
Date: 11
DOI: 10.1016/J.PLACENTA.2021.01.003
Abstract: Maternal asthma is known to impact intrauterine growth outcomes, which may be mediated, in part, by altered androgen signalling. Our aim was to explore whether the sheep placenta expresses androgen receptor (AR) isoforms and determine if the differential expression of AR protein isoforms is altered by maternal asthma. Four known AR isoforms were detected (AR-FL, AR-v1, AR-v7, and AR-45), and their expression and subcellular distribution was altered in the presence of maternal allergic asthma. These findings underscore the importance for in vivo models of maternal asthma to delineate molecular patterns that may contribute to feto-placental growth and development.
Publisher: Wiley
Date: 10-2019
DOI: 10.1113/JP278110
Publisher: Wiley
Date: 10-01-2021
Publisher: Wiley
Date: 27-12-2020
DOI: 10.1113/JP280693
Publisher: Wiley
Date: 29-03-2021
DOI: 10.1113/JP281002
Abstract: Human placental function is evaluated using non‐invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption ( ) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental by MRI was ∼4 ml min −1 kg −1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques. Our MRI approach can quantify uteroplacental , which involves the quantification of maternal‐ and fetal‐placental blood flows, fetal oxygen delivery and , and the oxygen gradient between uterine‐ and umbilical‐venous blood, providing a comprehensive assessment of placental function with clinical potential. It has not been feasible to perform routine clinical measurement of human placental oxygen consumption ( ) and in vitro studies do not reflect true metabolism in utero . Here we propose an MRI method to non‐invasively quantify in utero placental and fetal oxygen delivery ( ) and in healthy humans and sheep. Women ( n = 20) and Merino sheep ( n = 10 23 sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36 ± 2 weeks and 128 ± 9 days, respectively mean ± SD). Blood flow (phase‐contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine‐ and umbilical‐placental vessels, allowing calculation of uteroplacental and fetal and . Maternal (ml min −1 kg −1 fetus) to the gravid uterus was similar in humans and sheep (human = 54 ± 15, sheep = 53 ± 21, P = 0.854), while fetal (human = 25 ± 4, sheep = 22 ± 5, P = 0.049) was slightly lower in sheep. Uteroplacental and fetal (ml min −1 kg −1 fetus uteroplacental: human = 4.1 ± 1.5, sheep = 3.5 ± 1.9, P = 0.281 fetus: human = 6.8 ± 1.3, sheep = 7.2 ± 1.7, P = 0.426) were similar between species. Late gestational uteroplacental:fetal ratio did not change with age (human, P = 0.256 sheep, P = 0.121). Human umbilical blood flow (ml min −1 kg −1 fetus) decreased with advancing age ( P = 0.008), while fetal was preserved through an increase in oxygen extraction ( P = 0.046). By contrast, sheep fetal was preserved through stable umbilical flow (ml min −1 kg −1 P = 0.443) and oxygen extraction ( P = 0.582). MRI derived measurements of uteroplacental and fetal between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical ‘placental function test’.
Publisher: Cambridge University Press (CUP)
Date: 11-05-2022
DOI: 10.1017/S0007114521001549
Abstract: Diet is a modifiable risk factor for chronic disease and a potential modulator of telomere length (TL). The study aim was to investigate associations between diet quality and TL in Australian adults after a 12-week dietary intervention with an almond-enriched diet (AED). Participants (overweight/obese, 50–80 years) were randomised to an AED ( n 62) or isoenergetic nut-free diet (NFD, n 62) for 12 weeks. Diet quality was assessed using a Dietary Guideline Index (DGI), applied to weighed food records, that consists of ten components reflecting adequacy, variety and quality of core food components and discretionary choices within the diet. TL was measured by quantitative PCR in s les of lymphocytes, neutrophils, and whole blood. There were no significant associations between DGI scores and TL at baseline. Diet quality improved with AED and decreased with NFD after 12 weeks (change from baseline AED + 9·8 %, NFD − 14·3 % P 0·001). TL increased in neutrophils (+9·6 bp, P = 0·009) and decreased in whole blood, to a trivial extent (–12·1 bp, P = 0·001), and was unchanged in lymphocytes. Changes did not differ between intervention groups. There were no significant relationships between changes in diet quality scores and changes in lymphocyte, neutrophil or whole blood TL. The inclusion of almonds in the diet improved diet quality scores but had no impact on TL mid-age to older Australian adults. Future studies should investigate the impact of more substantial dietary changes over longer periods of time.
Publisher: American Physiological Society
Date: 07-2011
DOI: 10.1152/JAPPLPHYSIOL.00067.2011
Abstract: The development of the adult cardiac troponin complex in conjunction with changes in cardiac function and cardiomyocyte binucleation has not been systematically characterized during fetal life in a species where maturation of the cardiomyocytes occurs prenatally as it does in the human. The aim of this study was to correlate the expression of each of the major adult troponin isoforms (T, I, and C) during late gestation (term of 150 days) to changes in both Ca 2+ sensitivity and maximum Ca 2+ -activated force of the contractile apparatus and the maturation of cardiomyocytes. The percentage of mononucleated cardiomyocytes in the right ventricle decreased with gestational age to 46% by 137–142 days of gestation. The length of binucleated cardiomyocytes did not change with gestational age, but the length of binucleated cardiomyocytes relative to heart weight decreased with gestational age. There was no change in the expression of adult cardiac troponin T with increasing gestation. The contractile apparatus was significantly more sensitive to Ca 2+ at 90 days compared with either 132 or 139 days of gestation, consistent with an ∼30% increase in the expression of adult cardiac troponin I between 90 and 110 days of gestation. Maximum Ca 2+ -activated force significantly increased from 90 days compared with 130 days consistent with an increase of ∼40% in cardiac troponin C protein expression. These data show that increased adult cardiac troponin I and C protein expression across late gestation is consistent with reduced Ca 2+ sensitivity and increased maximum Ca 2+ -activated force. Furthermore, changes in cardiac troponin C, not I, protein expression track with the timing of cardiomyocyte binucleation.
Publisher: Wiley
Date: 19-07-2019
DOI: 10.1113/JP277629
Publisher: Wiley
Date: 16-03-2021
DOI: 10.1113/EP089237
Publisher: Informa UK Limited
Date: 06-2006
Publisher: Wiley
Date: 26-08-2021
DOI: 10.14814/PHY2.14999
Publisher: Wiley
Date: 29-05-2020
DOI: 10.1113/JP279725
Publisher: Wiley
Date: 28-08-2022
Abstract: Magnetic resonance imaging (MRI) assessment of fetal blood oxygen saturation (SO 2 ) can transform the clinical management of high‐risk pregnancies affected by fetal growth restriction (FGR). Here, a novel MRI method assesses the feasibility of identifying normally grown and FGR fetuses in sheep and is then applied to humans. MRI scans are performed in pregnant ewes at 110 and 140 days (term = 150d) gestation and in pregnant women at 28 +3 ± 2 +5 weeks to measure feto‐placental SO 2 . Birth weight is collected and, in sheep, fetal blood SO 2 is measured with a blood gas analyzer (BGA). Fetal arterial SO 2 measured by BGA predicts fetal birth weight in sheep and distinguishes between fetuses that are normally grown, small for gestational age, and FGR. MRI feto‐placental SO 2 in late gestation is related to fetal blood SO 2 measured by BGA and body weight. In sheep, MRI feto‐placental SO 2 in mid‐gestation is related to fetal SO 2 later in gestation. MRI feto‐placental SO 2 distinguishes between normally grown and FGR fetuses, as well as distinguishing FGR fetuses with and without normal Doppler in humans. Thus, a multi‐compartment placental MRI model detects low placental SO 2 and distinguishes between small hypoxemic fetuses and normally grown fetuses.
Publisher: Elsevier BV
Date: 2023
Publisher: American Physiological Society
Date: 15-03-2014
DOI: 10.1152/AJPREGU.00431.2013
Abstract: It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation. The mRNA expression and protein abundance of key factors regulating growth and metabolism were quantified using quantitative RT-PCR and Western blot analysis, respectively. Cardiac contractility was determined by measuring the Ca 2+ sensitivity and maximum Ca 2+ -activated force of skinned cardiomyocyte bundles. Rosiglitazone-treated fetuses had a lower cardiac abundance of insulin-signaling molecules, including insulin receptor-β, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 (Tyr-895), phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, PI3K catalytic subunit p110α, phospho-3-phosphoinositide-dependent protein kinase 1 (Ser-241), protein kinase B (Akt-1), phospho-Akt (Ser-273), PKCζ, phospho-PKCζ(Thr-410), Akt substrate 160 kDa (AS160), phospho-AS160 (Thr-642), and glucose transporter type-4. Additionally, cardiac abundance of regulators of fatty acid β-oxidation, including adiponectin receptor 1, AMPKα, phospho-AMPKα (Thr-172), phospho-acetyl CoA carboxylase (Ser-79), carnitine palmitoyltransferase-1, and PGC-1α was lower in the rosiglitazone-treated group. Rosiglitazone administration also resulted in a decrease in cardiomyocyte size. Rosiglitazone administration in the late-gestation sheep fetus resulted in a decreased abundance of factors regulating cardiac glucose uptake, fatty acid β-oxidation, and cardiomyocyte size. These findings suggest that activation of PPAR-γ using rosiglitazone does not promote the maturation of cardiomyocytes rather, it may decrease cardiac metabolism and compromise cardiac health later in life.
No related grants have been discovered for Stacey Holman.