Ellen Bennett

Lipids in yolks and neonates of the viviparous lizard Niveoscincus metallicus

Niveoscincus metallicus is a small viviparous skink which provides a substantial amount of yolk to each of its developing embryos although some organic nutrients are also transferred across the placentae. The total amount of lipid present in the yolk of N. metallicus (37% of dry weight) is very much higher than that in the newborns (19% of dry weight), confirming that the yolk is utilised as an energy source during gestation. Triacylglycerols (TAG), which are storage compounds, are the major lipid resource available to the embryos and are present in relatively large amounts in the yolk of N. metallicus. Polar lipids (PL), which form the structural components of membranes, and sterols (ST), which are involved in the synthesis of hormones and vitamins, are also present in the yolk. The proportions of each of these lipid classes differs markedly between yolks and newborns. This may reflect variations in the role played by each lipid class in the provision of nutrients to, and development of, embryos.

The independent effects of vitamin D deficiency and house dust mite exposure on lung function are sex-specific

Vitamin D deficiency is increasing around the world and has been associated with the development of asthma. This study aims to evaluate the effect of dietary vitamin D deficiency at different life stages on lung function using a murine model of allergic airways disease. BALB/c mice were challenged intranasally with HDM or saline alone for 10 days. Twenty four hours after the last challenge, mice were anesthetized and lung function was measured using the forced oscillation technique (FOT). Mice were euthanized for assessment of inflammation in the bronchoalveolar lavage (BAL) and total collagen content in lung homogenates by ELISA. Vitamin D deficiency impaired lung function in both male and female mice, increasing tissue damping and elastance, however had no effect on HDM induced inflammation. The impact of vitamin D deficiency was more evident in females. HDM also decreased airway distensibility, but only in females and this response was not altered by vitamin D deficiency. Our data suggest that vitamin D deficiency and HDM exposure have independent effects on lung mechanics and that females are more susceptible to these effects. Vitamin D deficiency may exacerbate lung function deficits by having a direct, but independent, effect on parenchymal mechanics.

Identification of vitamin D sensitive pathways during lung development

BackgroundWe have previously shown that vitamin D deficiency has a detrimental impact on lung development. In this study, we aimed to identify the mechanisms linking vitamin D with lung development using a mouse model of dietary manipulation.MethodsFemale offspring were euthanized at different time-points; embryonic day (E)14.5, E17.5 or postnatal day (P)7. Lung tissue was collected for mass spectrometry-based proteomic analysis. Label-free quantitation was used to identify the differentially expressed proteins and ELISA confirmed the expression of selected proteins. Lungs from separate groups of mice were fixed and processed for stereological assessment of lung structure.ResultsNo differences in protein expression between vitamin D deficient and replete mice were detected at E14.5 and E17.5, whereas 66 proteins were differentially expressed in P7 lungs. The expression of pulmonary surfactant-associated protein B (SP-B) and peroxiredoxin 5 (PRDX5) were reduced in P7 lungs of vitamin D deficient mice, while the production of collagen type Ι alpha 1 (COL1A1) was higher in lungs of vitamin D deficient mice. There were no differences in lung volume, parenchymal volume, volume of airspaces or surface area of airspaces between vitamin D deficient and vitamin D replete mice across three time-points.ConclusionsThe difference in protein expression during the early postnatal time-point suggests that vitamin D deficiency may induce alterations of lung structure and function in later life during alveolarization stage through impaired pulmonary surfactant production and anti-oxidative stress ability as well as enhanced collagen synthesis. These data provided a plausible mechanism linking maternal vitamin D deficiency with altered postnatal lung function.

Interrelationships among plasma progesterone concentrations, luteal anatomy and function, and placental ontogeny during gestation in a viviparous lizard (Niveoscincus metallicus: Scincidae)

Plasma progesterone concentrations were measured at six stages of gestation in the viviparous lizard Niveoscincus metallicus. Anatomical and functional parameters of luteal activity were also investigated. The diameter of the corpus luteum (CL) decreased gradually though gestation, as did the diameter of the luteal cells. Major degenerative changes were observed in CLs post-partum. Plasma progesterone concentrations were basal both prior to, and just after, ovulation; a rapid increase occurred in early gestation. Plasma progesterone concentrations remained elevated until late gestation, but fell some 2 weeks before parturition. In vitro production of progesterone was greater in CLs in mid- than in late-gestation, and the addition of prostaglandin F(2alpha) to the incubation medium had no effect on progesterone production. Non-luteal ovarian tissue and adrenals produced progesterone, but at approximately one-tenth the rate of production by CLs. Temporal correlations between the plasma progesterone profile and stages of placental development were also assessed. The rise in plasma progesterone concentrations occurs before differentiation of the chorioallantoic placenta, but progesterone is still high when it degenerates. We conclude that the CLs are the major source of gestational progesterone in N. metallicus.

Novel Analysis of 4DCT Imaging Quantifies Progressive Increases in Anatomic Dead Space During Mechanical Ventilation in Mice

Increased dead space is an important prognostic marker in early acute respiratory distress syndrome (ARDS) that correlates with mortality. The cause of increased dead space in ARDS has largely been attributed to increased alveolar dead space due to ventilation/perfusion mismatching and shunt. We sought to determine whether anatomic dead space also increases in response to mechanical ventilation. Mice received intratracheal lipopolysaccharide (LPS) or saline and mechanical ventilation (MV). Four-dimensional computed tomography (4DCT) scans were performed at onset of MV and after 5 h of MV. Detailed measurements of airway volumes and lung tidal volumes were performed using image analysis software. The forced oscillation technique was used to obtain measures of airway resistance, tissue damping, and tissue elastance. The ratio of airway volumes to total tidal volume increased significantly in response to 5 h of mechanical ventilation, regardless of LPS exposure, and airways demonstrated significant variation in volumes over the respiratory cycle. These findings were associated with an increase in tissue elastance (decreased lung compliance) but without changes in tidal volumes. Airway volumes increased over time with exposure to mechanical ventilation without a concomitant increase in tidal volumes. These findings suggest that anatomic dead space fraction increases progressively with exposure to positive pressure ventilation and may represent a pathological process.NEW & NOTEWORTHY We demonstrate that anatomic dead space ventilation increases significantly over time in mice in response to mechanical ventilation. The novel functional lung-imaging techniques applied here yield sensitive measures of airway volumes that may have wide applications.

A cross-sectional survey of environmental health in remote Aboriginal communities in Western Australia.

Abstract Introduction: The Australian Aboriginal population experiences significantly poorer health than the non-Aboriginal population. The contribution of environmental risk factors in remote communities to this health disparity is poorly understood. Objective: To describe and quantify major environmental risk factors and associated health outcomes in remote Aboriginal communities in Western Australia. Methods: The association between environmental health indicators, community infrastructure and reported health outcomes was analysed using linear and logistic regression of survey data. Results: Housing/overcrowding was significantly associated with increased reports of hearing/eyesight (OR 3.01 95 % CI 1.58–5.73), skin (OR 2.71 95 % CI 1.31–5.60), gastrointestinal (OR 3.51 95 % CI 1.49–8.26) and flu/colds (OR 2.47 95 % CI 1.27–4.78) as health concerns. Dust was significantly associated with hearing/eyesight (OR 3.16 95 % CI 1.82–5.48), asthma/respiratory (OR 2.48 95 % CI 1.43–4.29) and flu/colds (OR 3.31 95 % CI 1.88–5.86) as health concerns. Conclusion: Poor environmental health is prevalent in remote Aboriginal communities and requires further delineation to inform environmental health policy.

The Impact of Sex and 25(OH)D Deficiency on Metabolic Function in Mice

Both dietary fat and vitamin D deficiency have been linked with increased incidence of non-alcoholic fatty liver disease and insulin resistance. While sex differences in disease prevalence and severity are well known, the impact on disease pathogenesis remains unclear. To further explore the effect of these exposures on metabolic function, C57BL/6 male and female mice were weaned onto one of four diets; low fat vitamin D replete, low fat vitamin D deficient, or two high fat diets, one vitamin D replete and one deficient. Visceral fat, hepatic adiposity, and insulin resistance were measured after five and a half weeks. Vitamin D deficiency, independent of dietary fat, increased hepatic fat accumulation in both sexes (p = 0.003), although did not increase hepatic expression of interleukin-6 (p = 0.92) or tumor necrosis factor-α (p = 0.78). Males were observed to have greater insulin resistance (glucose area under the curve: p < 0.001, homeostatic model assessment for insulin resistance: p = 0.046), and have greater visceral adiposity (p < 0.001), while female mice had greater hepatic fat accumulation (p < 0.001). This study is the first to demonstrate vitamin D deficiency alone can cause hepatic accumulation while also being the first to observe higher liver fat percentages in female mice.

Maternal exposure to particulate matter alters early post-natal lung function and immune cell development

Background: In utero exposure to particulate matter (PM) from a range of sources is associated with adverse post‐natal health; however, the effect of maternal exposure to community‐sampled PM on early post‐natal lung and immune development is poorly understood. Objectives: Using a mouse model, we aimed to determine whether in utero exposure to PM alters early post‐natal lung function and immune cell populations. We used PM collected from ceiling voids in suburban houses as a proxy for community PM exposure. Methods: Pregnant C57BL/6 mice were intranasally exposed to ceiling derived PM, or saline alone, at gestational day (E) 13.5, 15.5, and 17.5. When mice were two weeks old, we assessed lung function by the forced oscillation technique, and enumerated T and B cell populations in the spleen and thymus by flow cytometry. Results: Maternal exposure to PM impaired somatic growth of male offspring resulting in reduced lung volume and deficits in lung function. There was no effect on thymic T cell populations in dams and their male offspring but PM decreased the CD4 +CD25 + T cell population in the female offspring. In contrast, maternal exposure to PM increased splenic CD3 +CD4 + and CD3 +CD8 + T cells in dams, and there was some evidence to suggest inhibition of splenic T cell maturation in male but not female offspring. Conclusions: Our findings suggested that maternal exposure to ceiling void PM has the capacity to impair early somatic growth and alter early life immune development in a sex specific manner. HighlightsIn utero exposure to PM impairs somatic growth and lung development in male offspring.In utero exposure to PM alters thymic T cell populations in female offspring.In utero exposure to PM is likely to increase the risk of post‐natal lung disease.