ORCID Profile
0000-0002-2914-7693
Current Organisation
University of Adelaide
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2016
DOI: 10.11124/JBISRIR-2016-003177
Abstract: The objective of this systematic review is to synthesize the best available evidence on the relationship between size at birth or fetal growth and postnatal allergy. Specifically, this review aims to assess evidence regarding relationships between absolute birth weight at term, birth weight corrected for gestational age, expressed as relative to population or customized growth data, or fetal growth measures and physician-diagnosed or parent- and self-reported postnatal clinical allergic disease (eczema/atopic dermatitis, hay fever/rhinitis, allergic asthma or anaphylaxis). The specific review question is: what is the association between the absolute birth weight at full-term or birth weight relative to population or customized data and corrected for gestational age or direct measures of fetal growth, and physician-diagnosed or parent- and self-reported clinical allergic disease (eczema/atopic dermatitis, hay fever/rhinitis, allergic asthma or anaphylaxis)?
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JRI.2017.07.002
Abstract: Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, a crude marker of the fetal environment, and allergy have been reported in humans and require comprehensive review. Associations between birth weight and allergy are however confounded in humans, and we and others have therefore begun exploring the effects of early life events on allergy in experimental models. In particular, we are using ovine models to investigate whether and how a restricted environment before birth protects against allergy, whether methyl donor availability contributes to allergic protection in IUGR, and why maternal asthma during pregnancy is associated with increased risks of allergic disease in children. We found that experimental intrauterine growth restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny, despite normal or elevated IgE responses. Furthermore, maternal methyl donor supplementation in late pregnancy partially reversed effects of experimental IUGR, consistent with the proposal that epigenetic pathways underlie some but not all effects of IUGR on allergic susceptibility. Ovine experimental allergic asthma with exacerbations reduces relative fetal size in late gestation, with some changes in immune populations in fetal thymus suggestive of increased activation. Maternal allergic asthma in mice also predisposes progeny to allergy development. In conclusion, these findings in experimental models provide direct evidence that a perturbed environment before birth alters immune system development and postnatal function, and provide opportunities to investigate underlying mechanisms and develop and evaluate interventions.
Publisher: Frontiers Media SA
Date: 28-07-2021
DOI: 10.3389/FPHYS.2021.718568
Abstract: Advanced maternal age (≥35 years old) increases the risk of pregnancy complications such as preecl sia and fetal growth restriction. We previously demonstrated vascular dysfunction and abnormal pregnancy outcomes in a rat model of advanced maternal age. However, vascular adaptations to pregnancy in aging were not studied. We hypothesize that advanced maternal age is associated with a more vasoconstrictive phenotype due to reduced nitric oxide (NO) and increased activity of matrix metalloproteinases (MMPs), contributing to impaired vascular adaptations to pregnancy. A rat model of advanced maternal age was used: young (4 months) and aged (9.5 months ∼35 years in humans) non-pregnant and pregnant rats. On gestational day 20 (term = 22 days non-pregnant rats were aged-matched), blood pressure and heart rate were measured (tail cuff plethysmography) and vascular function was assessed in mesenteric arteries (wire myography). Endothelium-dependent relaxation to methylcholine (MCh) was assessed in the presence/absence of nitric oxide synthase inhibitor (L-NAME), or inhibitors of endothelium-dependent hyperpolarization (EDH apamin and TRAM-34). Vasoconstriction responses to big endothelin-1 (bigET-1), in the presence/absence of MMPs-inhibitor (GM6001) or endothelin converting enzyme (ECE-1) inhibitor (CGS35066), in addition, ET-1 responsiveness, were measured. Blood pressure was elevated only in aged non-pregnant rats ( p & 0.001) compared to all other groups. MCh responses were not different, however, L-NAME decreased maximum vasodilation in young ( p & 0.01) and aged pregnant rats ( p & 0.001), and decreased MCh sensitivity in young non-pregnant rats ( p & 0.01), without effects in aged non-pregnant rats. EDH contribution to relaxation was similar in young non-pregnant, and aged non-pregnant and pregnant rats, while EDH-mediated relaxation was absent in young pregnant rats ( p & 0.001). BigET-1 responses were enhanced in aged non-pregnant ( p & 0.01) and pregnant rats ( p & 0.05). No significant changes in bigET-1 conversion occurred in the presence of MMP-inhibitor, whereas ECE-1 inhibition reduced bigET-1 constriction in aged rats ( p & 0.01). No differences in ET-1 sensitivity were observed. In conclusion, contrary to our hypothesis, reduced blood pressure, and an increased EDH-dependent contribution to vasodilation suggest a compensatory mechanism that may reflect beneficial adaptations in these aged rats that were able to maintain pregnancy. These data increase our understanding of how the vascular adaptive pathways in pregnancy compensate for advanced maternal age.
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: American Physiological Society
Date: 2018
DOI: 10.1152/AJPREGU.00549.2016
Abstract: Perinatal exposures are associated with altered risks of childhood allergy. Human studies and our previous work suggest that restricted growth in utero (IUGR) is protective against allergic disease. The mechanisms are not clearly defined, but reduced fetal abundance and altered metabolism of methyl donors are hypothesized as possible underlying mechanisms. Therefore, we examined whether late-gestation maternal dietary methyl donor and cofactor supplementation of the placentally restricted (PR) sheep pregnancy would reverse allergic protection in progeny. Allergic outcomes were compared between progeny from control pregnancies (CON n = 49), from PR pregnancies without intervention (PR n = 28), and from PR pregnancies where the dam was fed a methyl donor plus cofactor supplement from day 120 of pregnancy until delivery (PR + Methyl n = 25). Both PR and PR + Methyl progeny were smaller than CON supplementation did not alter birth size. PR was protective against cutaneous hypersensitivity responses to ovalbumin (OVA P 0.01 in singletons). Cutaneous hypersensitivity responses to OVA in PR + Methyl progeny were intermediate to and not different from the responses of CON and PR sheep. Cutaneous hypersensitivity responses to house dust mites did not differ between treatments. In singleton progeny, upper dermal mast cell density was greater in PR + Methyl than in PR or CON (each P 0.05). The differences in the cutaneous allergic response were not explained by treatment effects on circulating immune cells or antibodies. Our results suggest that mechanisms underlying in utero programming of allergic susceptibility by IUGR and methyl donor availability may differ and imply that late-gestation methyl donor supplementation may increase allergy risk.
Publisher: MDPI AG
Date: 28-06-2022
Abstract: Advanced maternal age (≥35 years) increases the risk of vascular complications in pregnancy that can result in fetal growth restriction and preecl sia. Endoplasmic reticulum (ER) stress has been linked to adverse pregnancy outcomes in these complicated pregnancies. However, the role of ER stress in advanced maternal age is not known. We hypothesize that increased ER stress contributes to altered vascular function and poor pregnancy outcomes, and that treatment with the ER-stress inhibitor TUDCA will improve pregnancy outcomes. First, young and aged non-pregnant regnant rats were used to assess ER stress markers in mesenteric arteries mesenteric artery phospho-eIF2α and CHOP expression were increased in aged dams compared to young dams. In a second study, young and aged control and TUDCA-treated dams were studied on gestational day (GD) 20 (term = 22 days). TUDCA treatment was provided via the drinking water throughout pregnancy (GD0-GD20 calculated dose of 150 mg/kg/day TUDCA). ER stress markers were quantified in mesenteric arteries, blood pressure was measured, pregnancy outcomes were recorded, mesenteric and main uterine arteries were isolated and vascular function was assessed by wire myography. Aged dams had increased phospho-eIF2α and CHOP expression, reduced fetal weight, reduced litter size, and impaired uterine artery relaxation. In the aged dams, TUDCA treatment reduced phospho-eIF2α and CHOP expression, reduced blood pressure, improved fetal body weight, and tended to improve uterine artery function compared to control-treated aged dams. In conclusion, our data illustrate the role of ER stress, as well as TUDCA as a potential therapeutic that may benefit pregnancy outcomes in advanced maternal age.
Publisher: American Physiological Society
Date: 04-2014
DOI: 10.1152/AJPREGU.00432.2013
Abstract: Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG 1 , and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control ( n = 40) pregnancies. Increases in circulating HDM-specific IgE ( P = 0.007) and OVA-specific IgE ( P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG 1 , or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only ( P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h ( P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons ( P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.
Publisher: Cambridge University Press (CUP)
Date: 26-05-2022
DOI: 10.1017/S2040174422000216
Abstract: Prenatal hypoxia is a common complication of pregnancy and is associated with detrimental health outcomes, such as impaired cardiac and vascular function, in adult offspring. Exposure to prenatal hypoxia reportedly impacts the reproductive system of female offspring. Whether exposure to prenatal hypoxia influences pregnancy adaptations and outcomes in these female offspring is unknown. We hypothesised that prenatal hypoxia impairs uterine artery adaptations in pregnancies of the adult offspring. Pregnancy outcomes and uterine artery function were assessed in 14–16 weeks old non-pregnant and late pregnant (gestational day 20 term = 22 days) adult female offspring born to rats exposed to prenatal normoxia (21% oxygen) or hypoxia (11% oxygen, between days 15–21 of gestation). Compared with normoxia controls, prenatal hypoxia was associated with pregnant adult offspring having reduced placental weights in their litters, and uterine artery circumferential stress that increased with pregnancy. Overall, prenatal hypoxia adversely, albeit mildly, compromised pregnancies of adult offspring.
Publisher: Cambridge University Press (CUP)
Date: 30-09-2016
DOI: 10.1017/S2040174416000477
Abstract: Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.
Publisher: Portland Press Ltd.
Date: 08-2023
DOI: 10.1042/BSR20230819
Abstract: Advanced maternal age (≥35 years) is a risk factor for poor pregnancy outcomes. Pregnancy requires extensive maternal vascular adaptations, and with age, our blood vessels become stiffer and change in structure (collagen and elastin). However, the effect of advanced maternal age on the structure of human resistance arteries during pregnancy is unknown. As omental resistance arteries contribute to blood pressure regulation, assessing their structure in pregnancy may inform on the causal mechanisms underlying pregnancy complications in women of advanced maternal age. Omental fat biopsies were obtained from younger (& years) or advanced maternal age (≥35 years) women during caesarean delivery (n = 7–9/group). Arteries (200–300 µm) were isolated and passive mechanical properties (circumferential stress and strain) assessed with pressure myography. Collagen (Masson’s Trichrome) and elastin (Verhoff) were visualized histologically and % positively-stained area was assessed. Median maternal age was 32 years (range 25–34) for younger, and 38 years (range 35–42) for women of advanced maternal age. Circumferential strain was lower in arteries from advanced maternal age versus younger women but circumferential stress was not different. Omental artery collagen levels were similar, while elastin levels were lower with advanced maternal age versus younger pregnancies. The collagen:elastin ratio was greater in arteries from advanced maternal age versus younger women. In conclusion, omental arteries from women of advanced maternal age were less compliant with less elastin compared with arteries of younger controls, which may affect how vascular stressors are tolerated during pregnancy. Understanding how vascular aging affects pregnancy adaptations may contribute to better pregnancy outcomes.
Publisher: Cambridge University Press (CUP)
Date: 06-04-2017
DOI: 10.1017/S2040174417000137
Abstract: Most in iduals whose growth was restricted before birth undergo accelerated or catch-up neonatal growth. This is an independent risk factor for later metabolic disease, but the underlying mechanisms are poorly understood. This study aimed to test the hypothesis that natural and experimentally induced in utero growth restriction increase neonatal appetite and milk intake. Control (CON) and placentally restricted (PR) ewes carrying multiple fetuses delivered naturally at term. Outcomes were compared between CON ( n =14) and PR ( n =12) progeny and within twin lamb pairs. Lamb milk intake and feeding behaviour and ewe milk composition were determined using a modified weigh-suckle-weigh procedure on days 15 and 23. PR lambs tended to have lower birth weights than CON (−15%, P =0.052). Neonatal growth rates were similar in CON and PR, whilst heavier twins grew faster in absolute but not fractional terms than their co-twins. At day 23, milk protein content was higher in PR than CON ewes ( P =0.038). At day 15, PR lambs had fewer suckling bouts than CON lambs and in females light twins had more suckling attempts than their heavier co-twins. Birth weight differences between twins positively predicted differences in milk intakes. Lactational constraint and natural prenatal growth restriction in twins may explain the similar milk intakes in CON and PR. Within twin comparisons support the hypothesis that prenatal constraint increases lamb appetite, although this did not increase milk intake. We suggest that future mechanistic studies of catch-up growth be performed in singletons and be powered to assess effects in each sex.
Publisher: Wiley
Date: 28-09-2020
DOI: 10.1113/JP280341
Abstract: Maternal shift work increases the risk of pregnancy complications, although its effects on progeny health after birth are not clear. We evaluated the impact of a simulated shift work protocol for one‐third, two‐thirds or all of pregnancy on the metabolic health of sheep progeny. Simulated shift work had no effect on growth, body size, body composition or glucose tolerance in pre‐pubertal or young adult progeny. Glucose‐stimulated insulin secretion was reduced in adult female progeny and insulin sensitivity was increased in adult female singleton progeny. The results of the present study do not support the hypothesis that maternal shift work exposure impairs metabolic health of progeny in altricial species. Disrupted maternal circadian rhythms, such as those experienced during shift work, are associated with impaired progeny metabolism in rodents. The effects of disrupted maternal circadian rhythms on progeny metabolism have not been assessed in altricial, non‐litter bearing species. We therefore assessed postnatal growth from birth to adulthood, as well as body composition, glucose tolerance, insulin secretion and insulin sensitivity, in pre‐pubertal and young adult progeny of sheep exposed to control conditions (CON: 10 males, 10 females) or to a simulated shift work (SSW) protocol for the first one‐third (SSW0‐7: 11 males, 9 females), the first two‐thirds (SSW0‐14: 8 males, 11 females) or all (SSW0‐21: 8 males, 13 females) of pregnancy. Progeny growth did not differ between maternal treatments. In pre‐pubertal progeny (12–14 weeks of age), adiposity, glucose tolerance and insulin secretion during an i.v. glucose tolerance test and insulin sensitivity did not differ between maternal treatments. Similarly, in young adult progeny (12–14 months of age), food intake, adiposity and glucose tolerance did not differ between maternal treatments. At this age, however, insulin secretion in response to a glucose bolus was 30% lower in female progeny in the combined SSW groups compared to control females ( P = 0.031), and insulin sensitivity of SSW0‐21 singleton females was 236% compared to that of CON singleton female progeny ( P = 0.025). At least in this model, maternal SSW does not impair progeny metabolic health, with some evidence of greater insulin action in female young adult progeny.
Publisher: Public Library of Science (PLoS)
Date: 06-04-2023
DOI: 10.1371/JOURNAL.PONE.0282442
Abstract: Advanced maternal age (≥35 years) is associated with an increased risk of pregnancy complications such as fetal growth restriction and preecl sia. We previously demonstrated poor pregnancy outcomes (reduced fetal body weight), altered vascular function, and increased expression of endoplasmic reticulum (ER) stress markers (phospho-eIF2α and CHOP) in mesenteric arteries from a rat model of advanced maternal age. Further, treatment of aged dams during pregnancy with an ER stress inhibitor, tauroursodeoxycholic acid (TUDCA) increased fetal body weight (both male and female), tended to improve uterine artery function, and reduced expression of phospho-eIF2α and CHOP in systemic arteries. Placental ER stress has been linked to poor pregnancy outcomes in complicated pregnancies but whether placental ER stress is evident in advanced maternal age is not known. In addition, sex-specific changes in the placental labyrinth and junctional zones from male and female offspring in advanced maternal age have not been investigated. Therefore, the current study aimed to investigate the effect of TUDCA intervention on placental ER stress. We hypothesize that placental ER stress is increased in a rat model of advanced maternal age that is alleviated by TUDCA intervention for both sexes. Placental ER stress markers (GRP78, phospho-eIF2α, ATF-4, CHOP, ATF-6α, and sXBP-1) were quantified by Western blot in placentas from male and female offspring the labyrinth and junction zones were analyzed separately. In the placental labyrinth zone from male offspring, only GRP78 (p = 0.007) was increased in aged dams compared to young dams TUDCA treatment reduced the placental expression of GRP78 in aged dams (p = 0.003). In addition, TUDCA reduced the levels of phospho-eIF2α (p = 0.021), ATF-4 (p = 0.016), and CHOP (p = 0.012) in aged dams but no effect was observed in young TUDCA-treated dams. In the placental labyrinth zone from female offspring, an increased level of phospho-eIF2α (p = 0.005) was observed in aged dams compared to young dams, and TUDCA treatment had no effect in both young and aged groups. In the placental junctional zone from male and female offspring, no changes in the expression of GRP78, phospho-eIF2α, ATF-4, CHOP, and ATF-6α was observed with or without TUDCA treatment in both young and aged groups, however, a reduced expression of sXBP-1 protein was observed in from both male (p = 0.001) and female (p = 0.031) placentas from aged-TUDCA treated dams compared to aged control. In conclusion, our data highlight the complexity and sex-specificity of ER stress responses in advanced maternal age with TUDCA treatment maintaining ER stress proteins to basal levels and improving fetal growth in both male and female offspring.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JACI.2019.08.032
Abstract: In idual susceptibility to allergic diseases is developmentally programmed by early-life exposures. Evidence from preclinical studies suggests that intrauterine growth restriction is protective against later inflammatory responses to allergens. We sought to evaluate whether prenatal growth affects susceptibility to allergy in human subjects. We systematically searched for relevant studies in 11 databases, including Web of Science, ProQuest, EMBASE, and PubMed. We included only studies that corrected for gestational age or were restricted to full-term infants to separate effects of fetal growth from those of prematurity. The 42 eligible studies included prospective and retrospective cohort, cross-sectional, and case-control studies. Only 2 studies reported allergic asthma. A birth weight increase of 1 kg was associated with a 44% greater risk of food allergy in children (odds ratio [OR], 1.44 95% CI, 1.04-1.99 P = .001), a 17% greater risk of ever allergic dermatitis in children (OR, 1.17 95% CI, 1.04-1.32 P = .008), and a 34% greater risk of ever or current allergic dermatitis in infants up to 2 years of age (OR, 1.34 95% CI, 1.08-1.68 P = .009). Risks of allergic rhinitis were not associated with birth weight. The results of these meta-analyses suggest that intrauterine growth restriction protects against allergic diseases in human subjects consistent with preclinical evidence but that effects might differ between allergic diseases. The strongest evidence is available for infancy and early childhood, and additional studies in older children and adults are needed to determine whether the effects of prenatal growth on each allergic disease persist or differ between those with severe and mild phenotypes.
Publisher: Cambridge University Press (CUP)
Date: 23-06-2016
DOI: 10.1017/S2040174416000283
Abstract: Intrauterine growth restriction (IUGR) has adverse effects on metabolic health and early life, whereas physical activity is protective against later development of metabolic disease. Relationships between birth weight and physical activity in humans, and effects of IUGR on voluntary activity in rodents, are mixed and few studies have measured physical activity in a free-ranging environment. We hypothesized that induced restriction of placental growth and function (PR) in sheep would decrease spontaneous ambulatory activity (SAA) in free-ranging adolescent and young adult progeny from multi-fetal pregnancies. To test this hypothesis, we used Global Positioning System watches to continuously record SAA between 1800 and 1200 h the following day, twice during a 16-day recording period, in progeny of control (CON, n =5 males, 9 females) and PR pregnancies ( n =9 males, 10 females) as adolescents (30 weeks) and as young adults (43 weeks). PR reduced size at birth overall, but not in survivors included in SAA studies. In adolescents, SAA did not differ between treatments and females were more active than males overall and during the day (each P .001). In adults, daytime SAA was greater in PR than CON females ( P =0.020), with a similar trend in males ( P =0.053) and was greater in females than males ( P =0.016). Adult SAA was negatively correlated with birth weight in females only. Contrary to our hypothesis, restricted placental function and small size at birth did not reduce progeny SAA. The mechanisms for increased daytime SAA in adult female PR and low birth weight sheep require further investigation.
Publisher: American Physiological Society
Date: 15-09-2015
DOI: 10.1152/AJPENDO.00487.2014
Abstract: Intrauterine growth restriction (IUGR) increases the risk of adult type 2 diabetes (T2D) and obesity. Neonatal exendin-4 treatment can prevent diabetes in the IUGR rat, but whether this will be effective in a species where the pancreas is more mature at birth is unknown. Therefore, we evaluated the effects of neonatal exendin-4 administration after experimental restriction of placental and fetal growth on growth and adult metabolic outcomes in sheep. Body composition, glucose tolerance, and insulin secretion and sensitivity were assessed in singleton-born adult sheep from control (CON n = 6 females and 4 males) and placentally restricted pregnancies (PR n = 13 females and 7 males) and in sheep from PR pregnancies that were treated with exendin-4 as neonates (daily sc injections of 1 nmol/kg exendin-4 PR + exendin-4 n = 11 females and 7 males). Placental restriction reduced birth weight (by 29%) and impaired glucose tolerance in the adult but did not affect adult adiposity, insulin secretion, or insulin sensitivity. Neonatal exendin-4 suppressed growth during treatment, followed by delayed catchup growth and unchanged adult adiposity. Neonatal exendin-4 partially restored glucose tolerance in PR progeny but did not affect insulin secretion or sensitivity. Although the effects on glucose tolerance are promising, the lack of effects on adult body composition, insulin secretion, and insulin sensitivity suggest that the neonatal period may be too late to fully reprogram the metabolic consequences of IUGR in species that are more mature at birth than rodents.
Publisher: MDPI AG
Date: 16-08-2022
DOI: 10.3390/IJMS23169191
Abstract: Advanced maternal age (≥35 years) is associated with pregnancy complications. Aging impairs vascular reactivity and increases vascular stiffness. We hypothesized that uterine artery adaptations to pregnancy are impaired with advanced age. Uterine arteries of nonpregnant and pregnant (gestational day 20) young (4 months) and aged (9 months ~35 years in humans) Sprague-Dawley rats were isolated. Functional (myogenic tone, n = 6–10/group) and mechanical (circumferential stress-strain, n = 10–24/group) properties were assessed using pressure myography and further assessment of elastin and collagen (histology, n = 4–6/group), and matrix metalloproteinase-2 (MMP-2, zymography, n = 6/group). Aged dams had worse pregnancy outcomes, including smaller litters and fetal weights (both p 0.0001). Only in arteries of pregnant young dams did higher pressures ( mmHg) cause forced vasodilation. Across the whole pressure range (4–160 mmHg), myogenic behavior was enhanced in aged vs. young pregnant dams (p = 0.0010). Circumferential stress and strain increased with pregnancy in young and aged dams (p 0.0001), but strain remained lower in aged vs. young dams (p 0.05). Arteries from young nonpregnant rats had greater collagen:elastin ratios than the other groups (p 0.05). In aged rats only, pregnancy increased MMP-2 active capacity. Altered functional and structural vascular adaptations to pregnancy may impair fetal growth and development with advanced maternal age.
Publisher: Wiley
Date: 03-07-2019
DOI: 10.1113/JP277952
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000443961
Abstract: b i Background: /i /b Around 30-40% of the world's population will experience allergy, the most common and earliest-onset noncommunicable disease. With a steady rise in the incidence of allergic disease over recent decades, up to 18% of children will suffer a respiratory, food or skin allergy before their 18th birthday. There is compelling evidence that the risk of developing allergy is influenced by early life events and particularly in utero exposures. b i Methods: /i /b A comprehensive literature review was undertaken which outlines prenatal risk factors and potential mechanisms underlying the development of allergy in childhood. b i Results: /i /b Exposures including maternal cigarette smoking, preterm birth and Caesarean delivery are implicated in predisposing infants to the later development of allergy. In contrast, restricted growth in utero, a healthy maternal diet and a larger family size are protective, but the mechanisms here are unclear and require further investigation. b i Conclusion: /i /b To ameliorate the allergy pandemic in young children, we must define prenatal mechanisms that alter the programming of the fetal immune system and also identify specific targets for antenatal interventions.
Location: Australia
No related grants have been discovered for Amy Wooldridge.