Placental metabolism: substrate requirements and the response to stress

The placenta is a dynamic, metabolically active organ with significant nutrient and energy requirements for growth, nutrient transfer and protein synthesis. It uses a range of substrates to meet its energy needs and has a higher rate of oxygen (O2) consumption than many other foetal and adult tissues. Placental metabolism varies with species and alters in response to a range of nutritional and endocrine signals of adverse environmental conditions. The placenta integrates these signals and adapts its metabolic phenotype to help maintain pregnancy and to optimize offspring fitness by diversifying the sources of carbon and nitrogen available for energy production, hormone synthesis and foeto-placental growth. The metabolic response of the placenta to adversity depends on the nature, severity and duration of the stressful challenge and on whether the insult is maternal, placental or foetal in origin. This review examines placental metabolism and its response to stresses common in pregnancy with particular emphasis on farm species like the sheep. It also considers the consequences of changes in placental metabolism for the supply of O2 and nutrients to the foetus.The authors are grateful to the CTR and the Biotechnology and Biological Sciences Research Council for research funding

Dexamethasone treatment of pregnant F0 mice leads to parent of origin-specific changes in placental function of the F2 generation.

Dexamethasone treatment of F0 pregnant rodents alters F1 placental function and adult cardiometabolic phenotype. The adult phenotype is transmitted to the F2 generation without further intervention, but whether F2 placental function is altered by F0 dexamethasone treatment remains unknown. In the present study, F0 mice were untreated or received dexamethasone (0.2µgg(-1)day(-1), s.c.) over Days 11-15 or 14-18 of pregnancy (term Day 21). Depending on the period of F0 dexamethasone treatment, F1 offspring were lighter at birth or grew more slowly until weaning (P<0.05). Glucose tolerance (1gkg(-1), i.p.) of adult F1 males was abnormal. Mating F1 males exposed prenatally to dexamethasone with untreated females had no effect on F2 placental function on Day 19 of pregnancy. In contrast, when F1 females were mated with untreated males, F2 placental clearance of the amino acid analogue (14)C-methylaminoisobutyric acid was increased by 75% on Day 19 specifically in dams prenatally exposed to dexamethasone on Days 14-18 (P<0.05). Maternal plasma corticosterone was also increased, but F2 placental Slc38a4 expression was decreased in these dams (P<0.05). F0 dexamethasone treatment had no effect on F2 fetal or placental weights, regardless of lineage. Therefore, the effects of F0 dexamethasone exposure are transmitted intergenerationally to the F2 placenta via the maternal, but not paternal, line.This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1071/RD14285

Hypoxia, fetal and neonatal physiology: 100 years on from Sir Joseph Barcroft.

This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27200

A physiological increase in maternal cortisol alters uteroplacental metabolism in the pregnant ewe

Fetal nutrition is determined by maternal availability, placental transport and uteroplacental metabolism of carbohydrates. Cortisol affects maternal and fetal metabolism, but whether maternal cortisol concentrations within the physiological range regulate uteroplacental carbohydrate metabolism remains unknown. This study determined the effect of maternal cortisol infusion (1.2 mg kg−1 day−1 I.V. for 5 days, n = 20) on fetal glucose, lactate and oxygen supplies in pregnant ewes on day 130 of pregnancy (term = 145 days). Compared to saline infusion (n = 21), cortisol infusion increased maternal, but not fetal, plasma cortisol (P < 0.05). Cortisol infusion also raised maternal insulin, glucose and lactate concentrations, and blood pH, PCO2 and HCO3 − concentration. Although total uterine glucose uptake determined by Fick’s principle was unaffected, a greater proportion was consumed by the uteroplacental tissues, so net fetal glucose uptake was 29% lower in cortisol-infused than control ewes (P < 0.05). Concomitantly, uteroplacental lactate production was > 2-fold greater in cortisol- than saline-treated ewes (P < 0.05), although uteroplacental O2 consumption was unaffected by maternal treatment. Materno-fetal clearance of non-metabolizable [3H]methyl-D-glucose and placental SLC2A8 (glucose transporter 8) gene expression were also greater with cortisol treatment. Fetal plasma glucose, lactate or α-amino nitrogen concentrations were unaffected by treatment although fetal plasma fructose and hepatic lactate dehydrogenase activity were greater in cortisol- than saline-treated ewes (P < 0.05). Fetal plasma insulin levels and body weight were also unaffected by maternal treatment. During stress, cortisol-dependent regulation of uteroplacental glycolysis may allow increased maternal control over fetal nutrition and metabolism. However, when maternal cortisol concentrations are raised chronically, prolonged elevation of uteroplacental lactate production may compromise fetal wellbeing

A physiological increase in maternal cortisol alters uteroplacental metabolism in the pregnant ewe.

KEY POINTS: Fetal nutrient supply is dependent, in part, upon the transport capacity and metabolism of the placenta. The stress hormone, cortisol, alters metabolism in the adult and fetus but it is not known whether cortisol in the pregnant mother affects metabolism of the placenta. In this study, when cortisol concentrations were raised in pregnant sheep by infusion, proportionately more of the glucose taken up by the uterus was consumed by the uteroplacental tissues while less was transferred to the fetus, despite an increased placental glucose transport capacity. Concomitantly, the uteroplacental tissues produced lactate at a greater rate. The results show that maternal cortisol concentrations regulate uteroplacental glycolytic metabolism, producing lactate for use in utero. Prolonged increases in placental lactate production induced by cortisol overexposure may contribute to the adverse effects of maternal stress on fetal wellbeing. ABSTRACT: Fetal nutrition is determined by maternal availability, placental transport and uteroplacental metabolism of carbohydrates. Cortisol affects maternal and fetal metabolism, but whether maternal cortisol concentrations within the physiological range regulate uteroplacental carbohydrate metabolism remains unknown. This study determined the effect of maternal cortisol infusion (1.2 mg kg(-1)  day(-1) i.v. for 5 days, n = 20) on fetal glucose, lactate and oxygen supplies in pregnant ewes on day ∼130 of pregnancy (term = 145 days). Compared to saline infusion (n = 21), cortisol infusion increased maternal, but not fetal, plasma cortisol (P  2-fold greater in cortisol- than saline-treated ewes (P < 0.05), although uteroplacental O2 consumption was unaffected by maternal treatment. Materno-fetal clearance of non-metabolizable [(3) H]methyl-d-glucose and placental SLC2A8 (glucose transporter 8) gene expression were also greater with cortisol treatment. Fetal plasma glucose, lactate or α-amino nitrogen concentrations were unaffected by treatment although fetal plasma fructose and hepatic lactate dehydrogenase activity were greater in cortisol- than saline-treated ewes (P < 0.05). Fetal plasma insulin levels and body weight were also unaffected by maternal treatment. During stress, cortisol-dependent regulation of uteroplacental glycolysis may allow increased maternal control over fetal nutrition and metabolism. However, when maternal cortisol concentrations are raised chronically, prolonged elevation of uteroplacental lactate production may compromise fetal wellbeing

Virtual Reality and Physical Models in Undergraduate Orthopaedic Education: A Modified Randomised Crossover Trial.

Background: Orthopaedic surgery is underrepresented in the United Kingdom medical school curriculum, with an average of less than 3 weeks of exposure over the five-year degree. This study evaluates the effectiveness of high-fidelity virtual reality (VR) and physical model simulation in teaching undergraduate orthopaedic concepts. Methods: A modified randomised crossover trial was used. Forty-nine students were randomly allocated to two groups, with thirty-three finishing the six-week follow-up assessment. All undergraduate medical students were eligible for inclusion. Both groups were given introductory lectures, before completing a pre-test with questions on the principles of fracture fixation and osteotomy. Each group then received a lecture on these topics with the same content, but one was delivered with VR and the other with physical models. Both groups completed the post-course assessments. Knowledge was assessed by way of questionnaire immediately before, immediately after, and six-weeks after. Results: In the VR group, participants improved their post-training score by 192.1% (U=32; p<0.00001). In the physical models group, participants improved their post-training scores by 163.1% (U=8.5; p<0.00001). Overall, there was no statistically significant difference in the total means of post-training test scores between the VR and the physical models study groups (U=260.5; p=0.4354). Conclusion: Both VR and physical models represent valuable educational adjuncts for the undergraduate medical curriculum. Both have demonstrated improvements in immediate and long-term knowledge retention of key orthopaedic concepts

Boys to Men: A Conference Report

Nearly 350 middle and high school aged boys, fathers and male mentors attended. It was the first such conference to be held in Maine. “Boys to Men” was intended to launch a community dialogue about how schools, families and other institutions can better understand, celebrate and support boys in their journey to manhood. There was a special emphasis on the pressures exerted by popular culture in shaping the behavior of adolescent boys

Genome sequence of the entomopathogenic Serratia entomophila isolate 626 and characterisation of the species specific itaconate degradation pathway

Background: Isolates of Serratia entomophila and S. proteamaculans (Yersiniaceae) cause disease specifc to the endemic New Zealand pasture pest, Costelytra giveni (Coleoptera: Scarabaeidae). Previous genomic profling has shown that S. entomophila isolates appear to have conserved genomes and, where present, conserved plasmids. In the absence of C. giveni larvae, S. entomophila prevalence reduces in the soil over time, suggesting that S. entomophila has formed a host-specifc relationship with C. giveni. To help define potential genetic mechanisms driving retention of the chronic disease of S. entomophila, the genome of the isolate 626 was sequenced, enabling the identifcation of unique chromosomal properties, and defining the gain/loss of accessory virulence factors relevant to pathogenicity to C. giveni larvae. Results: We report the complete sequence of S. entomophila isolate 626, a causal agent of amber disease in C. giveni larvae. The genome of S. entomophila 626 is 5,046,461 bp, with 59.1% G+C content and encoding 4,695 predicted CDS. Comparative analysis with five previously sequenced Serratia species, S. proteamaculans 336X, S. marcescens Db11, S. nematodiphila DH-S01, S. grimesii BXF1, and S. ficaria NBRC 102596, revealed a core of 1,165 genes shared. Further comparisons between S. entomophila 626 and S. proteamaculans 336X revealed fewer predicted phage-like regions and genomic islands in 626, suggesting less horizontally acquired genetic material. Genomic analyses revealed the presence of a four-gene itaconate operon, sharing a similar gene order as the Yersinia pestis ripABC complex. Assessment of a constructed 626::RipC mutant revealed that the operon confer a possible metabolic advantage to S. entomophila in the initial stages of C. giveni infection. Conclusions: Evidence is presented where, relative to S. proteamaculans 336X, S. entomophila 626 encodes fewer genomic islands and phages, alluding to limited horizontal gene transfer in S. entomophila. Bioassay assessments of a S. entomophila-mutant with a targeted mutation of the itaconate degradation region unique to this species, found the mutant to have a reduced capacity to replicate post challenge of the C. giveni larval host, implicating the itaconate operon in establishment within the host

The application of deep eutectic solvent ionic liquids for environmentally-friendly dissolution and recovery of precious metals

publisher: Elsevier articletitle: The application of deep eutectic solvent ionic liquids for environmentally-friendly dissolution and recovery of precious metals journaltitle: Minerals Engineering articlelink: http://dx.doi.org/10.1016/j.mineng.2015.09.026 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.© 2015 Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)