1,721,013 research outputs found
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
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
New perspectives on placental fatty acid transfer
No full textThe human foetus depends on placental transfer for the fatty acids required for its growth and development. Long chain polyunsaturated fatty acids (LC-PUFAs) may specifically influence neurodevelopment. Therefore, it is important to understand the mechanisms of placental transfer of LC-PUFAs. The simple view of placental fatty acid transfer is that it occurs by diffusion down the maternal to foetal gradient, facilitated by membrane transporters. This view has been complicated by studies highlighting the role of placental metabolism in fatty acid transfer. Most fatty acids taken up by the placenta will be esterified and incorporated into lipid rather than diffusing directly across to the foetus. Furthermore, this esterification is likely to mean that placental intracellular “free” fatty acid concentrations are lower than in foetal plasma which would not be conducive to simple diffusion of fatty acids to the foetus. Placental structure poses additional questions, in particular how fatty acids cross the hydrophilic villous stroma separating the trophoblast from the endothelium and how they cross the endothelium itself. The understanding of placental fatty acid transfer needs to evolve to address these questions. The role of the placenta is not simply to mediate solute transfer; it is also a central endocrine organ of pregnancy. Placental-derived lipid mediators, such as prostaglandins, have well-established roles in parturition and, almost certainly, throughout gestation. Metabolic targeting of specific fatty acids to different lipid pools in the placenta may determine their availability as both nutrients and signalling molecules. Placental transfer will determine fatty acid availability within the foetus as well as influencing maternal levels. Fatty acids and their derivatives may also act as signals to the placenta indicating metabolic states in both mother and foetus. Placental uptake and metabolism of LC-PUFAs are important to meet both foetal and placental demands. This paper will review placental fatty acid transfer and metabolism and highlight issues which need to be addressed.</p
The role of the placenta in the developmental origins of health and disease: implications for practice
No full textThe placenta is actively involved in transporting nutrients to the fetus, it has both direct and indirect effects on fetal cardiovascular function and has endocrine influences on the mother and fetus. As such, a properly functioning placenta is crucial for normal fetal development and plays a central role in mediating effects of the maternal environment on the fetus. An altered external environment or abnormal placental function can induce developmental changes in the fetus and may have important consequences for the risk of cardiovascular and metabolic disease in adult life.The developmental origins hypothesis proposes that the early environment, from the periconceptional period until early childhood, can predispose an individual to adult cardiovascular and metabolic disease. This hypothesis is supported by epidemiological studies and by work in animals. These effects do not just act in low birth weight babies but have been shown to occur within the normal range of birth weight. It is thought that fetal adaptations to an impaired intra-uterine environment may enhance survival in early life but have deleterious effects in later life.Experimental studies suggest that maternal diet and body composition can alter placental structure and function, and we have recently demonstrated associations between a woman's nutritional state before pregnancy and placental function at term. To elucidate these relationships, further work is needed to define markers of placental function and to characterize their relation to rates of fetal growth.Understanding how the placenta mediates maternal influences will be crucial in determining the mechanisms underlying developmental programming. This will allow the design of targeted public health interventions, both before and during pregnancy, to enhance placental function and thereby improve the health of the offspring throughout life
Placental fatty acid transfer
No full textPURPOSE OF REVIEW: This review outlines recent advances in placental lipid transport in relation to maternal metabolic status and pregnancy outcome. A particular focus of this review will be on the way these findings may influence our understanding of placental transfer of the essential fatty acid docosahexaenoic acid (DHA) which is crucial for fetal neurodevelopment and of lipid transfer as a predisposing factor for childhood obesity.RECENT FINDINGS: Placental metabolism may determine the quantity and composition of fatty acids delivered to the fetus. Maternal factors, such as obesity, appear to regulate placental lipid metabolism and may influence fatty acids delivery to the fetus. Although the role of placental metabolism is now recognized, new evidence also suggests important roles for nontraditional fatty acid transporters such as Mfsd2a which facilitates transfer of DHA.SUMMARY: Placental lipid metabolism is likely to be a determinant of placental transfer of fatty acids to the fetus. Maternal conditions, such as obesity, have now been shown to regulate placental lipid metabolism and thus may influence fatty acid transfer and fetal development. However, it is not yet clear how regulation of placental lipid metabolism affects fatty acid delivery to the fetus and its long-term health.</p
Umbilical venous-arterial plasma composition differences suggest differential incorporation of fatty acids in NEFA and cholesteryl ester pools
Get PDFThe developing fetus requires an adequate supply of fatty acids, in particular PUFA, for optimal growth and development. Little is known about the transfer of fatty acids by the placenta into the fetal circulation. However, the molecular form in which fatty acids are transferred into the fetal circulation may influence their metabolism and hence their availability to specific tissues. The aim of the present study was to determine which lipid pools in the fetal circulation become enriched in fatty acids from the placenta by comparing the fatty acid compositions of individual lipid pools between umbilical venous (UV) and umbilical arterial (UA) plasma. Plasma from the UV and UA was collected after delivery from ten uncomplicated pregnancies, and the fatty acid composition of each lipid class was determined by GC. Total NEFA concentration in the UV was twofold higher than in the UA (P < 0·05) due to enrichment in 16 : 0, 16 : 1n-7, 18 : 1n-9, 18 : 1n-7, 18 : 2n-6, 20 : 3n-6, 20 : 4n-6, 24 : 0 and 22 : 6n-3. Total cholesteryl ester concentration was twofold higher in the UV than in the UA (P < 0·05) due to enrichment in 16 : 0, 16 : 1n-7, 18 : 0, 18 : 1n-9, 18 : 1n-7, 18 : 2n-6 and 20 : 4n-6. There were no significant UV–UA differences in the total concentration or composition of TAG or phosphatidylcholine. The present study demonstrates differential enrichment across the placenta of fatty acids into specific lipid pools in the fetal circulation. Such partitioning may facilitate supply of individual fatty acids to specific fetal tissues
The influence of placental metabolism on fatty acid transfer to the fetus
No full textThe factors determining fatty acid transfer across the placenta are not fully understood. This study used a combined experimental and computational modeling approach to explore placental transfer of nonesterified fatty acids and identify the rate-determining processes. Isolated perfused human placenta was used to study the uptake and transfer of 13C-fatty acids and the release of endogenous fatty acids. Only 6.2 ± 0.8% of the maternal 13C-fatty acids taken up by the placenta was delivered to the fetal circulation. Of the unlabeled fatty acids released from endogenous lipid pools, 78 ± 5% was recovered in the maternal circulation and 22 ± 5% in the fetal circulation. Computational modeling indicated that fatty acid metabolism was necessary to explain the discrepancy between uptake and delivery of 13C-fatty acids. Without metabolism, the model overpredicts the fetal delivery of 13C-fatty acids 15-fold. Metabolic rate was predicted to be the main determinant of uptake from the maternal circulation. The microvillous membrane had a greater fatty acid transport capacity than the basal membrane. This study suggests that incorporation of fatty acids into placental lipid pools may modulate their transfer to the fetus. Future work needs to focus on the factors regulating fatty acid incorporation into lipid pools
Estrone sulphate uptake by the microvillous membrane of placental syncytiotrophoblast is coupled to glutamate efflux
No full textOrganic anion transporters (OATs) and organic anion transporting polypeptides (OATPs) are transport proteins that mediate exchange of metabolites, hormones and waste products. Directional transport by these transporters can occur when exchange is coupled to the gradients of other substrates. This study investigates whether the activity of OATP4A1 and OATP2A1 on the maternal facing microvillus membrane of the placental syncytiotrophoblast is coupled to the glutamate gradient. OAT and OATP transporter proteins were over expressed in Xenopus oocytes to study their transport characteristics. Further transport studies were performed in term human placental villous fragments. Xenopus oocytes expressing OATP4A1 mediated glutamate uptake. No glutamate transport was observed in oocytes expressing OAT1, OAT3, OAT7 or OATP2A1. In oocytes expressing OATP4A1, uptake of estrone sulphate, thyroid hormones T3 and T4 and the bile acid taurocholate stimulated glutamate efflux. In term placental villous fragments addition of estrone sulphate and taurocholate trans-stimulated glutamate efflux. Coupling of OATP4A1 to the glutamate gradient may drive placental uptake of estrone-sulphate and thyroid hormone while also facilitating uptake of potentially harmful bile acids. In contrast, if OATP2A1 is not coupled to a similar gradient, it may function more effectively as an efflux transporter, potentially mediating efflux of prostaglandins to the mother. This study provides further evidence for glutamate as an important counter-ion driving transport into the placenta.</p
Low serine hydroxymethyltransferase activity in the human placenta has important implications for fetal glycine supply
No full textGlycine is essential for fetal development, but in both sheep and human pregnancy, little is transported directly from the mother to the fetus, indicating that fetal glycine is derived from other sources. In the sheep, placental conversion of maternal serine by serine hydroxymethyltransferase (SHMT) provides almost all the glycine transported to the fetus. Although mRNA for mitochondrial and cytoplasmic SHMT has been detected in human placenta, it is not known whether substantial placental conversion of serine to glycine occurs in species other than sheep. We determined SHMT activity in human, rat, and sheep placenta by measuring conversion of [3-14C]serine to 14C-methylene tetrahydrofolate. Compared with term human placenta, SHMT activity per gram of placenta was 5.1-fold higher in term rat placenta and 24.1-fold higher in term sheep placenta. In sheep placenta, SHMT activity per gram of placenta increased 2.1-fold between mid-gestation and term. In human placenta, placental SHMT activity was similar 8 wk post conception and at term. The low activity of SHMT in the human and rat placenta suggests that, unlike in the sheep, placental conversion of serine to glycine is not a major source of fetal glycine in these species
Computational modelling of amino acid transfer interactions in the placenta
No full textAmino acid transfer from mother to fetus via the placenta plays a critical role in normal development, and restricted transfer is associated with fetal growth restriction. Placental amino acid transfer involves the interaction of 15 or more transporters and 20 amino acids. This complexity means that knowing which transporters are present is not sufficient to predict how they operate together as a system. Therefore, in order to investigate how placental amino acid transfer occurs as a system an integrated mathematical/computational modelling framework was developed to represent the simultaneous transport of multiple amino acids. The approach was based on a compartmental model, in which separate maternal, syncytiotrophoblast and fetal volumes were distinguished, and transporters were modelled on the maternal and fetal facing membranes of the syncytiotrophoblast using Michaelis-Menten type kinetics. The model was tested in comparison with placental perfusion experiments studying serine-alanine exchange and found to correspond well. The results demonstrated how the different transporters can work together as an integrated system and allowed their relative importance to be assessed. Placental/fetal serine exchange was found to be most sensitive to basal membrane transporter characteristics, but a range of secondary less intuitive effects were also revealed. While this work only addressed a relatively simple 3 amino acid system it demonstrates the feasibility of the approach and could be extended to incorporate additional experimental parameters. Ultimately this approach will allow physiological simulations of amino acid transfer. This will enhance our understanding of these complex systems and placental function in health and disease
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