1,721,065 research outputs found
Dataset for The influence of placental metabolism on fatty acid transfer to the fetus
No full textDataset supporting:
Perazzolo, Simone, Sengers, Bram and Lewis, Rohan (2016) The influence of placental metabolism on fatty acid transfer to the fetus. The Journal of Lipid Research.</span
Multiscale three-dimensional imaging of the placenta
No full textPlacental function involves multiple different processes which operate at different scales from centimetres to nanometres. Everything that the placenta does from mediating blood flow to gene expression, occurs within a three-dimensional anatomical framework. This review outlines how multiscale three-dimensional imaging approaches can provide insight into placental structure and function. Three-dimensional imaging approaches include microCT, confocal, super resolution, light-sheet, and serial block-face scanning electron microscopy. Used together, these approaches allow three-dimensional imaging of the placenta across the scales at which different processes occur. Three-dimensional imaging illustrates the spatial relationships between structures and visualises structures that are not clearly apparent in two-dimensions. Understanding the three-dimensional structure of the placenta enables exploration of the relationship between structure and function, including through the development of computational models based on realistic geometries. Three-dimensional imaging approaches will enhance our understanding of placental function in health and disease
Computational modelling of placental amino acid transfer as an integrated system
No full textPlacental amino acid transfer is essential for fetal development and its impairment is associated with poor fetal growth. Amino acid transfer is mediated by a broad array of specific plasma membrane transporters with overlapping substrate specificity. However, it is not fully understood how these different transporters work together to mediate net flux across the placenta. Therefore the aim of this study was to develop a new computational model to describe how human placental amino acid transfer functions as an integrated system. Amino acid transfer from mother to fetus requires transport across the two plasma membranes of the placental syncytiotrophoblast, each of which contains a distinct complement of transporter proteins. A compartmental modelling approach was combined with a carrier based modelling framework to represent the kinetics of the individual accumulative, exchange and facilitative classes of transporters on each plasma membrane. The model successfully captured the principal features of transplacental transfer. Modelling results clearly demonstrate how modulating transporter activity and conditions such as phenylketonuria, can increase the transfer of certain groups of amino acids, but that this comes at the cost of decreasing the transfer of others, which has implications for developing clinical treatment options in the placenta and other transporting epithelia.
The work using this model was published as: Pantichob et al, Computational modelling of placental amino acid transfer as an integrated system, BBA - Biomembranes 2016, accepted, http://dx.doi.org/10.1016/j.bbamem.2016.03.028</span
Placental perfusion and mathematical modelling
No full textThe isolated perfused placental cotyledon technique has led to numerous advances in placental biology. Combining placental perfusion with mathematical modelling provides an additional level of insight into placental function. Mathematical modelling of perfusion data provides a quantitative framework to test the understanding of the underlying biology and to explore how different processes work together within the placenta as part of an integrated system. The perfusion technique provides a high degree of control over the experimental conditions as well as regular measurements of functional parameters such as pressure, solute concentrations and pH over time. This level of control is ideal for modelling as it allows placental function to be studied across a wide range of different conditions which permits robust testing of mathematical models. By placing quantitative values on different processes (e.g. transport, metabolism, blood flow), their relative contribution to the system can be estimated and those most likely to become rate-limiting identified. Using a combined placental perfusion and modelling approach, placental metabolism was shown to be a more important determinant of amino acid and fatty acid transfer. In contrast, metabolism was a less important determinant of placental cortisol transfer than initially thought. Identifying the rate-limiting factors in the system allows future work to be focused on the factors that are most likely to underlie placental dysfunction. A combined experimental and modelling approach using placental perfusions promotes an integrated view of placental physiology that can more effectively identify the processes leading to placental pathologies
The placental exposome, placental epigenetic adaptations and lifelong cardio-metabolic health.
No full textThe placental exposome represents the sum of all placental exposures, and through its influence on placental function can affect an individual's susceptibility to cardio-metabolic disease later in life. The placental exposome includes direct exposures during gestation, as well as those prior to gestation that affect the gametes or aspects of maternal physiology that influence placental function. This review will discuss the evidence for placental responses to environmental signals and its involvement in programming offspring health. A wide range of exposures may influence the placenta including maternal metabolic and endocrine status, nutrition, stress and toxins. Epigenetic changes within the placenta induced by these exposures may mediate persistent effects on placental function. Identifying which exposures are most influential in terms of placental function and offspring health is key to focusing future research and developing stratified and personalised interventions
High placental inositol content associated with suppressed pro-adipogenic effects of maternal glycaemia in offspring: the GUSTO cohort
No full textBackground/Objectives: Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels. Methods: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks’ gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed. Results: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted β [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [−21.2, 183.2], AAT = 0.8 ml [−8.4, 10.0]). Conclusions: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.</p
Dataset for Modelling the effect of intervillous flow on solute transfer based on 3D imaging of the human placental microstructure
No full textComsol files used for the simulations presented in the following paper:
Simone Perazzolo, Rohan Lewis, Bram Sengers, Modelling the effect of intervillous flow on solute transfer based on 3D imaging of the human placental microstructure. Placenta 2017.</span
Placental lipid and fatty acid transfer in maternal overnutrition
No full textBACKGROUND: The increasing incidence of childhood obesity is a significant public health challenge, the consequences of which extend across the life course.SUMMARY: Diet and exercise are clearly the major contributors to childhood obesity, but the factors predisposing to obesity may become established in the womb. Worryingly maternal overnutrition, in particular when it leads to obesity and diabetes, perpetuate an intergenerational cycle of obesity through its effects on placental function and fetal metabolism. This review will address the ways in which the placental lipid and fatty acid transfer may lay the foundations for obesity in the context of maternal overnutrition. Key Messages: (1) Metabolic changes associated with maternal obesity affect placental nutrient handling. (2) Altered placental nutrient handling may induce pro-adipogenic changes in the fetus, in particular increased fetal insulin. (3) Understanding the effects of maternal obesity on the placenta will aid the development of effective interventions to optimise pregnancy outcomes.</p
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