1,720,975 research outputs found
The mechanisms and regulation of placental amino acid transport to the human foetus
No full textThe mechanisms by which amino acids are transferred across the human placenta are fundamental to our understanding of foetal nutrition. Amino acid transfer across the human placenta is dependent on transport across both the microvillous and basal plasma membranes of the placental syncytiotrophoblast, and on metabolism within the syncytiotrophoblast. Although the principles underlying uptake of amino acids across the microvillous plasma membrane are well understood, the extent to which amino acids are metabolised within human placenta and the mechanisms by which amino acids are transported out of the placenta across the basal plasma membrane are not well understood. Understanding the mechanisms and regulation of amino acid transport is necessary to understand the causes of intrauterine growth restriction in human pregnancy
Placenta, evolution and lifelong health
No full textThe intrauterine environment has an important influence on lifelong health, and babies who grew poorly in the womb are more likely to develop chronic diseases in later life. Placental function is a major determinant of fetal growth and is therefore also a key influence on lifelong health. The capacity of the placenta to transport nutrients to the fetus and regulate fetal growth is determined by both maternal and fetal signals. The way in which the placenta responds to these signals will have been subject to evolutionary selective pressures. The responses selected are those which increase Darwinian fitness, i.e. reproductive success. This review asks whether in addition to responding to short-term signals, such as a rise in maternal nutrient levels, the placenta also responds to longer-term signals representing the mother’s phenotype as a measure of environmental influences across her life course. Understanding how the placenta responds to maternal signals is therefore not only important for promoting optimal fetal growth but can also give insights into how human evolution affected developmental history with long-term effects on health and disease
Sex differences in the mRNA levels of housekeeping genes in human placenta
No full textIn our recent letter to Placenta we reported the expression stability of mRNA for 12 potential housekeeping genes in placental tissue using the geNorm system [1] J.K. Cleal, P. Day, M.A. Hanson and R.M. Lewis, Measurement of housekeeping genes in human placenta, Placenta (2009).[1]. We identified three which had the most stable mRNA expression and recommended these for use in studies on human placenta.We have subsequently analysed the mRNA levels of these housekeeping genes by quantitative real-time rtPCR in 102 human placentas from the Southampton Women’s Survey [2]. With the larger sample size it became apparent that all three housekeeping genes were expressed at a higher level in male placentas (n = 53) than in female placentas (n = 49): UBC 19.8 (18.6–20.9) vs 17.8 (16.3–19.3), p = 0.035; TOP1 22.8 (21.7–23.8) vs 19.7 (18.4–20.9), p = 0.0002; YWHAZ 19.25 (18.4–20.1) vs 17.6 (16.7–18.6), p = 0.014, data is mean and 95% CI (arbitrary units) in male and female placentas respectively. This interesting observation has implications for our understanding of placental biology as well as questioning the suitability of these genes for use as housekeeping genes where male and female placentas are being analysed together.<br/
Characterisation of amino acid efflux across the human placental syncytiotrophoblast basal membrane
No full textThe effect of acute maternal hypoglycaemia on fetal cardiovascular control
No full textAims: To investigate the effect of acute maternal hypoglycaemia
on fetal cardiovascular (CV) function, as a sub-optimal environment
in utero has been implicated in the development of CV disease in
adult life.Subjects: Fetal sheep (n = 7) were studied in utero at 125 and 126
days gestational age (dGA, term = 147 days) following implantation
of vascular catheters and an umbilical cord occluder at 119 dGA.Study design: Fetal CV parameters were measured during a
maternal saline (day 125) and insulin (day 125) infusion. Fetal
CV function was assessed by: (a) generating a dose response
curve to angiotensin II; (b) a 90 sec total umbilical cord occlusion;
(c) administration of phenylephrine to assess baroreflex function.Outcome measures: (a) Area under the mean arterial blood
pressure (MAP) response (AUC) to increasing doses of angiotensin II;
(b) MAP and heart rate (HR) response to cord occlusion;
(c) sensitivity and operating point of the baroreflex response.
Results: Maternal insulin infusion resulted in maternal and fetal
hypoglycaemia. (a) The angiotensin II MAP AUC was not affected
by hypoglycaemia. (b) The increase in MAP and decrease in
HR following a 90 sec cord occlusion was not affected by
hypoglycaemia. (c) Hypoglycaemia resulted in reduced fetal
baroreflex sensitivity (P <0.05, paired t test).Conclusions: Our finding of reduced fetal baroreflex sensitivity
during fetal hypoglycaemia indicates altered CV homeostatic
mechanisms. Such fetal adaptations to a poor intrauterine
environment could contribute towards the development of altered
cardiovascular phenotype in adult life
What factors determine placental glucose transfer kinetics?
No full textIntroduction: transfer of glucose across the human placenta is directly proportional to maternal glucose concentrations even when these are well above the physiological range. This study investigates the relationship between maternal and fetal glucose concentrations and transfer across the placenta.Methods: transfer of d-glucose, 3H-3-o-methyl-d-glucose (3H-3MG) and 14C-l-glucose across the isolated perfused human placental cotyledon was determined for maternal and fetal arterial d-glucose concentrations between 0 and 20 mmol/l.Results: clearance of 3H-3MG or 14C-l-glucose was not affected by maternal or fetal d-glucose concentrations in either circulation.Discussion: based on the arterial glucose concentrations and the reported KM for GLUT1, the transfer of d-glucose and 3H-3MG would be expected to show signs of saturation as d-glucose concentrations increased but this did not occur. One explanation for this is that incomplete mixing of maternal blood and the rate of diffusion across unstirred layers may lower the effective concentration of glucose at the microvillous membrane and subsequently at the basal membrane. Uncertainties about the affinity of GLUT1 for glucose, both outside and inside the cell, may also contribute to the difference between the predicted and observed kinetics.Conclusion: these factors may therefore help explain why the observed and predicted kinetics differ and they emphasise the importance of understanding the function of transport proteins in their physiological context. The development of a computational model of glucose transfer may improve our understanding of how the determinants of placental glucose transfer interact and function as a syste
Hypothalamo-pituitary-adrenal axis responsiveness in adult sheep following early life nutrient restriction
No full textNon-invasive measures of heart rate variability following intermittent umbilical cord occlusion in the preterm ovine fetus
No full textEarly-life undernutrition induces sex-specific effects on the sympatho-adrenal response to stress in sheep
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