Placental Function (placental + function)

Distribution by Scientific Domains

Selected Abstracts

Computational modelling of amino acid transfer interactions in the placenta

B. G. Sengers
Amino 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 three 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. [source]

Divergent effects of ephedrine and phenylephrine on cardiovascular hemodynamics of near-term fetal sheep exposed to hypoxemia and maternal hypotension

T. Erkinaro
Background:, We hypothesized that the administration of ephedrine and phenylephrine for maternal hypotension modifies cardiovascular hemodynamics in near-term sheep fetuses. Methods:, At 115,136 days of gestation, chronically instrumented, anesthetized ewes with either normal placental function or increased placental vascular resistance after placental embolization were randomized to receive boluses of ephedrine (n = 12) or phenylephrine (n = 12) for epidural-induced hypotension after a short period of hypoxemia. Fetal cardiovascular hemodynamics were assessed by Doppler ultrasonography at baseline, during hypotension and after vasopressor treatment. Results:, During hypotension, fetal PO2 decreased and proximal branch pulmonary arterial and pulmonary venous vascular impedances increased. Additionally, in the embolized fetuses, the time-velocity integral ratio between the antegrade and retrograde blood flow components of the aortic isthmus decreased. These parameters were restored to baseline conditions by ephedrine but not by phenylephrine. With phenylephrine, weight-indexed left ventricular cardiac output and ejection force decreased in the non-embolized fetuses, and the proportion of isovolumetric contraction time of the total cardiac cycle was elevated in the embolized fetuses. Conclusions:, After exposure to hypoxemia and maternal hypotension, ephedrine restored all fetal cardiovascular hemodynamic parameters to baseline. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus observed in fetuses with increased placental vascular resistance. Moreover, fetal left ventricular function was impaired during phenylephrine administration. [source]

FGF Ligand Family mRNA Expression Profile for Mouse Preimplantation Embryos, Early Gestation Human Placenta, and Mouse Trophoblast Stem Cells

W. Zhong
Abstract Signaling by fibroblast growth factor (FGF) is essential is for trophoblast stem (TS) cells and preimplantation embryos. FGF4 provides essential signaling, but the expression of the complete set of 23 FGF family members has not been analyzed. Here, semi-quantitative RT-PCR and microarray analyses were used to define expression of all FGF ligand mRNA. RT-PCR was done for developmentally important FGF subfamilies, FGF10/FGF22 and FGF8/FGF17/FGF18 as well as FGF11. FGF4 and FGF18 are detected at highest levels by RT-PCR and microarrays. FGF10 was detected at low levels in both assays. FGF11 was detected at moderate levels by microarray, but not by RT-PCR. FGF17 was detected at low levels by array and moderate levels by RT-PCR. FGF8 and FGF22 were detected by RT-PCR, but not by microarrays during late cleavage divisions. FGF8, FGF5, and FGF9 were detected in the oocyte by microarray. FGF2, FGF3, and FGF7 were not detected by RT-PCR or microarrays and FGF13, FGF14, and FGF23 were not detected by microarray. Since a major role of FGF is to maintain TS cells, we tested human and mouse placental cell lines and early gestation human placenta for expression of FGF ligands. Expression in mouse TS cells was compared with preimplantation embryos, and human placental cell line expression was compared with human placenta, to infer which ligands are expressed in placental lineage vs. other cell lineages. The data suggest that human and mouse placenta share FGF18 and its high expression suggests preimplantation and early placental function. Mol. Reprod. Dev. 2006 Wiley-Liss, Inc. [source]

Abnormal Expression of TIMP-2, SOD, Vimentin and PAI Proteins in Cloned Bovine Placentae

H-R Kim
Contents Cloned mammals suffer from high rates of placental abnormality and foetal loss during pregnancy. We previously used 2-D gel electrophoresis and mass spectrometry for global proteomic analysis of cloned and normal bovine placentae to identify differential protein expression patterns. Here, we used Western blot analysis to confirm the expression levels of several pregnancy-related proteins putatively identified as being differentially expressed in somatic cell nuclear transfer (SCNT) vs normal bovine placentae. The expression levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), its downstream protein, matrix metalloproteinase-2 (MMP-2), superoxide dismutase (SOD), vimentin and plasminogen activator inhibitor-1 (PAI) were analysed in the placentae of SCNT cloned Korean native cattle that died immediately after birth and in normal placentae obtained by AI. Our results revealed that TIMP-2 and SOD were up-regulated in SCNT placenta compared with normal placenta, whereas MMP-2 levels were comparable in cloned and normal placentae, and vimentin and PAI were significantly down-regulated in SCNT compared with normal placentae. Our results suggest that key proteins of placental development are abnormally expressed in SCNT cloned bovine placentae, probably resulting in abnormal placental function and clonal mortality. [source]

Placental insulin-like growth factor II (IGF-II) and its relation to litter size in the common marmoset monkey (Callithrix jacchus)

Julienne N. Rutherford
Abstract The primate placenta produces a wide variety of hormones throughout gestation that regulate placental function and fetal growth. One such hormone is insulin-like growth factor-II (IGF-II), a peptide implicated in cell division, differentiation, and amino acid transport. IGF-II concentrations were measured in 23 common marmoset (Callithrix jacchus) term placentas from twin and triplet litters in order to determine whether previously described differences in fetoplacental phenotype such as placental and litter mass and placental surface area were related to differences in endocrine function. IGF-II was extracted from frozen tissue samples and measured using an enzyme-linked immunosorbent assay kit designed for human tissue, which was validated for marmoset placenta. IGF-II concentrations were not related to placental or litter mass, and twin and triplet placentas did not differ in total concentration. However, per individual fetus, triplets were associated with a significant 42% reduction in IGF-II concentration (P=0.03), and IGF-II concentration per gram of fetal mass was a third lower in triplet litters. The triplet placenta exhibits a global expansion of the surface area which was contrasted by a per unit area reduction in IGF-II concentration (r=,0.75, P=0.01), a pattern that explains why twin and triplet placentas overall did not differ in concentration. Per fetus, triplet pregnancies are associated with relatively less maternal mass, placental mass and microscopic surface area suggesting that the intrauterine growth of triplets is supported by systems that increase the efficiency of nutrient transfer. The finding that individual triplet fetuses are also associated with significantly lower IGF-II concentrations is consistent with the view that the marmoset fetoplacental unit exhibits a flexible pattern of placental allocation and metabolism. Plasticity in placental endocrine and metabolic function is likely to play an important role in the ability of the fetus to sense and accommodate the intrauterine environment and, by extension, the external ecology. Am. J. Primatol. 71:969,975, 2009. 2009 Wiley-Liss, Inc. [source]

REVIEW ARTICLE: Medawar Redux , An Overview on the Use of Farm Animal Models to Elucidate Principles of Reproductive Immunology

Peter J. Hansen
Citation Hansen PJ. Medawar redux , an overview on the use of farm animal models to elucidate principles of reproductive immunology. Am J Reprod Immunol 2010 Farm animals have been important models for the development of reproductive immunology. Two of the major concepts underpinning reproductive immunology, the idea of the fetal allograft and progesterone's role in regulation of uterine immunity, were developed using the bovine as a model. This volume of the American Journal of Reproductive Immunology is composed of review articles that highlight the continued relevance of farm animals as models for research in mammalian biology. It is important that a diverse array of genotypes are used to elucidate biological principles relevant to mammalian biology and human health because the nature of mammalian evolution has resulted in a situation where the genome of the most commonly used animal model, the laboratory mouse, is less similar to the human than other species like the cow. Moreover, the evolution of placental function has been accompanied by formation of new genes during recent evolution so that orthologs do not exist in any but closely related species. Given the infrastructure needs to study farm animal species, optimal utilization of these animals as models for biomedical research will require significant increases in funding to reverse a historical erosion of resources devoted to animal agricultural research. [source]

Biology of the prolactin family in bovine placenta.


ABSTRACT The placenta produces various peptides and steroid hormones that regulate placental function and fetal growth. Prolactin-related proteins are peptides that are produced by the placenta and belong to the growth hormone/prolactin family, and have structural similarity to prolactin and placental lactogen. Although several prolactin-related protein genes have been detected in bovine placenta, their expression profiles and functions are not clear. The main difficulties in examining their biological function is the similarity between their genes and the lack of information about their proteins. Recently, molecular biology methods have been used to detect some new bovine prolactin-related proteins, and elucidate their biological functions. This review focuses on the structures, expression profiles and conceivable functions of prolactin-related proteins in bovine placenta. With respect to their expression profiles, bovine prolactin-related proteins fall into four groups: (i) those expressed around the implantation period; (ii) those that reach peak expression in the middle of gestation; (iii) those that increase with the progress of gestation, reaching a peak in late gestation; and (iv) those that reach a plateau in early gestation and are maintained at that level throughout gestation. Data indicate that bovine prolactin-related proteins have different biological roles in different periods of gestation. ,In situ monitoring suggests that bovine prolactin-related protein-I has a role in the attachment of trophoblast cells to endometrium during the early implantation period. [source]

Fetal nutrition: A review

Irene Cetin
Abstract Knowledge of fetal nutrient supply has greatly increased in the last decade due to the availability of fetal blood samples obtained under relatively steady-state conditions. These studies, together with studies utilizing stable isotope methodologies, have clarified some aspects of the supply of the major nutrients for the fetus such as glucose, amino acids and fatty acids. At the same time, the relevance of intrauterine growth has been recognized not only for the well-being of the neonate and child, but also for later health in adulthood. The major determinants of fetal nutrient availability are maternal nutrition and metabolism together with placental function and metabolism. The regulation of the rate of intrauterine growth is the result of complex interactions between genetic inheritance, endocrine environment and availability of nutrients to the fetus. [source]

Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placenta

Charles Marseille-Tremblay
Abstract Maternal hypercholesterolemia (HC) during pregnancy and gestational diabetes mellitus (GDM) are associated with disturbance of fetal development which may also modify key features of placental functions. In this study, we evaluated the impact of maternal hypercholesterolemia on placental cholesterol and lipid metabolism in 59 women classified in two groups according to the median concentration of plasma total cholesterol (6.42 mM). The impact of GDM was also evaluated on the metabolism of placentas obtained from 7 insulin-treated GDM and 7 non-GDM women. We showed that high maternal circulating cholesterol is associated with a significant increase in the LDL-cholesterol, ApoB-100 and triglyceride concentrations in the maternal blood. However the level of cholesterol in the venous cord blood and placenta remains unchanged in response to modification in maternal cholesterol profile. The levels of Fatty acid synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in the HC group while expression of both sterol regulatory element-binding proteins-1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified. GDM is not associated with modification in the maternal lipid profile but it increases the concentration of inflammatory cytokines (IL-1, and TNF-,) in placenta which correlates with a dramatic induction of FAS expression without affecting the expression of mature SREBPs proteins. In conclusion, our study suggests that in placenta, expressions of key proteins involved in de novo lipid synthesis are affected by changes in maternal metabolism (HC and GDM) that may subsequently affect fetal development. Mol. Reprod. Dev. 75: 1054,1062, 2007. 2007 Wiley-Liss, Inc. [source]