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Query: UMLS:C0028754 (obesity)
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Most frequently, placental glycogen has been studied as an index of fetal nutrition. There are no published studies of placental glycogen as an index of fetal stress. In this study of 1573 samples from 71 placentae, glycogen levels in the placental disk, fetal membranes and umbilical cord of normal uncomplicated pregnancies were compared with those in complicated pregnancies. The complicated pregnancies included preterm delivery, hypertensive disorders, inadequate prenatal care, substance abuse, maternal fever or infection, obesity, diabetes mellitus, premature rupture of membranes, intrauterine growth retardation, sickle cell trait, and acute meconium staining of amniotic fluid at delivery. The data showed that the only significant differences were in the subgroup complicated by meconium-stained amniotic fluid in which the placental disks and umbilical cords had significantly lower (P=0.0006) glycogen levels. This finding suggests a relatively specific association. It is interesting to speculate that the passage of meconium with its vasoconstrictive effect increases utilization of local glycogen stores, decreases local glycogen reserves needed for the work of further vasoconstriction, and, in the event of subsequent acute stress, impairs vascular perfusion of tissues. In this way, meconium could predispose the infant to asphyxia.
Placenta 1998 May
PMID:Decreased placental and umbilical cord glycogen levels associated with meconium-stained amniotic fluid. 963 25

Leptin is an endocrine and a growth factor which is important for regulation of body fat, feeding, and energy homeostasis. The anti-obesity function of leptin has been recently extended to reproduction, puberty and pregnancy as an endocrine signal to the hypothalamus. Leptin controls the functional integrity of the feto-placental unit thereby maintaining pregnancy by virtue of its immunomodulatory property via T lymphocytes or other proto-oncogenes. Dysregulation of autocrine/paracrine function of leptin at feto-placento-maternal interface may be implicated in the pathogenesis of recurrent miscarriage gestational diabetes, pre-eclampsia and intra-uterine fetal growth retardation including disturbance of fetal bone turnover. This review will focus on the role of leptin in normal and abnormal pregnancy and fetal growth.
Placenta
PMID:Prospective function of placental leptin at maternal-fetal interface. 1194 77

Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05). We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg. Resistin is a novel adipocyte-derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.
Placenta 2002 Apr
PMID:Role of leptin in pregnancy--a review. 1197 63

Throughout its entire lifespan, the placenta is able to produce as well as respond to a variety of inflammatory stimuli. Many signaling molecules and concurrent pathways responsible for the propagation of an inflammatory response have been identified in placental cells. From early developmental stages onward, the secretory activity of placenta cells clearly contributes to increase local as well as systemic levels of cytokines and inflammatory molecules. Two aspects of the progression of an immune response have been particularly investigated: the highly regulated process of invasion and implantation and, the induction of preterm labor associated with infections. With the progression of pregnancy, the physiological role of most placental cytokines is more uncertain. Many placental cytokines are similar to adipose tissue derived cytokines. One possibility is that they contribute to the low grade systemic inflammation developing during the third trimester of pregnancy. The prevalent hypothesis is that activation of some inflammatory pathways is necessary to induce maternal insulin resistance which is required for the progression of normal gestation. As an integrative organ, the placenta may relay or enhance the contribution made by the cells of the adipose tissue and immune system in non-pregnant individuals. In pregnancy complicated with obesity or diabetes mellitus, continuous adverse stimulus is associated with dysregulation of metabolic, vascular and inflammatory pathways supported by increased circulating concentration of inflammatory molecules. It is believed that maternal adipose tissue and placental cells both contribute to the inflammatory situation by releasing common molecules. For example, the accumulation of leptin and TNF-alpha is associated with an increased production for markers of inflammation, fibrotic response, vascular remodeling and proteins facilitating lipid storage within the placenta.
Placenta 2006 Aug
PMID:The placenta cytokine network and inflammatory signals. 1624 70

During pregnancy, the developing fetus is dependent on its mother for all nutritional requirements. It is not surprising, therefore, that variations in maternal nutrition can be reflected in alterations in fetal health and well-being. Interestingly, the changes can persist into adulthood and may result in increased risk of diseases such as diabetes, obesity and cardiovascular disease. The first observations of these phenomena resulted in the development of hypotheses collectively brought under the heading of "fetal" or, more recently, "developmental" programming. In this review, we will examine some of the animal models used to understand the mechanisms involved and attempt to determine whether there are common, "gatekeeper", pathways or genes, altered by the different nutritional stresses. We will concentrate primarily on nutrition related to post-natal development of hypertension and will restrict the review to studies in rodents, since that is where most of the mechanistic studies are being undertaken. Our conclusions are that, while there may well be some common gatekeeper pathways, there is also some diversity of mechanism which may contribute to the generation of the same or similar phenotypes.
Placenta 2006 Apr
PMID:Fetal programming: causes and consequences as revealed by studies of dietary manipulation in rats -- a review. 1653 23

Research on intrauterine growth restriction (IUGR) and subsequent development of obesity, type 2 diabetes and the metabolic syndrome is rapidly expanding, and potential implications for primary prevention are considerable. We have critically appraised one of the experimental animal models frequently used as mimic of human fetal growth restriction, which involves bilateral ligation of the uterine artery in rats (Lig). Our experimental study showed that Lig performed on day 17 of pregnancy neither leads to IUGR nor to neonatal catch-up growth, an important pathogenetic co-factor in humans. Meta-analysis of the literature revealed domination by studies in which Lig pups with IUGR were actively selected. Accordingly, publication bias is evident (p=0.007). Altered placental perfusion--the main cause of IUGR in humans in Western countries--neither led to IUGR nor to neonatal catch-up growth in Lig offspring, i.e., to none of the etiological factors of the human 'small baby syndrome'. Appropriate and reproducible rodent models of IUGR through decreased placental flow remain to be established to uncover the pathophysiological basis of the 'small baby syndrome'. This may lead to new strategies of primary prevention of diabetes, obesity, and the metabolic syndrome.
Placenta 2008 Mar
PMID:Intrauterine growth restriction in a rodent model and developmental programming of the metabolic syndrome: a critical appraisal of the experimental evidence. 1820 35

Obesity and pregnancy are associated with a combination of insulin resistance and inflammatory changes which exacerbate in combination. Based on the similarity between the inflammatory transcriptomes of adipose tissue and placenta, we hypothesized that the placenta develops exaggerated inflammation in response to obesity. The aim of this study was to characterize placental inflammatory mediators and macrophage accumulation in relation to peripheral inflammation in obesity. Placental macrophages and maternal peripheral blood mononuclear cells (PBMC) from 20 obese and 15 lean women were functionally and phenotypically characterized using immunohistochemistry, flow cytometry and expression for macrophage markers and inflammatory cytokines. The number of resident CD68+ and CD14+ cells was increased 2-3 fold in the placenta of obese as compared to lean women. The macrophage population was characterized by a marked phenotypic heterogeneity with complex subsets of CD14+, CD68+ and CD11b+ (mac-1) cells and by an increased expression of the pro-inflammatory cytokines IL-1, TNF-alpha, IL-6. Placental inflammation was associated with an activation of PBMC gene expression with an increase in the monocyte differentiation and maturation markers CD14 and CD68 in maternal but not fetal PBMC. The inflammatory changes were associated with higher plasma concentrations of C-reactive protein and IL-6 in obese compared to lean women. In conclusion, the chronic inflammation state of pre-gravid obesity is extending to in utero life with accumulation of a heterogeneous macrophage population and pro-inflammatory mediators in the placenta. The resulting inflammatory milieu in which the fetus develops may have critical consequences for short and long term programming of obesity.
Placenta 2008 Mar
PMID:Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. 1826 44

Maternal obesity is an increasing problem in obstetrics associated with adverse pregnancy outcomes and delivery complications. As an inflammatory state, where elevated levels of pro-inflammatory cytokines are found, obesity can lead to the increased incidence of oxidative and nitrative stress. These stresses may result in protein oxidation and protein nitration respectively, which are post- translational covalent modifications that can modify the structure and subsequently alter the function of a protein. The objective of this study was to examine whether placental oxidative and nitrative stress increase with increasing maternal body mass index. Placental tissue was collected from three groups of patients categorized as lean, overweight and obese. The presence of nitrotyrosine residues, a marker of nitrative stress, and antioxidant enzymes, as markers of oxidative stress, were assessed by immunohistochemistry, Western blot and ELISA. Protein carbonyl formation, a specific measure of protein oxidation, was measured by OxyBlot kit. Nitrotyrosine residues were increased in obese compared to lean and overweight groups although localization was unaltered across the three groups. Superoxide dismutase enzyme expression, localization and activity was unaltered between the groups. Protein carbonyl formation was greater in the lean compared to the overweight individuals. This study demonstrates that with increasing maternal body mass index there is an increase in placental nitrative stress. There does not appear to be a corresponding increase in oxidative stress and indeed we demonstrate some evidence of a decrease in oxidative effects in these placenta samples. Potentially the formation of peroxynitrite may be consuming reactive oxygen species and reducing oxidative stress. There may be a shift in the balance between nitrative and oxidative stress, which may be a protective mechanism for the placenta.
Placenta 2009 Feb
PMID:Effect of increasing maternal body mass index on oxidative and nitrative stress in the human placenta. 1910 Jun 19

Maternal obesity is present in 20-34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes in the placenta. The major findings of this study were: 1) decreased placental syncytiotrophoblast amplification factor, intact syncytiotrophoblast endoplasmic reticulum structure and decreased system A placental amino acid transport in obese animals; 2) fetal serum amino acid composition and mononuclear cells (PBMC) transcriptome were different in fetuses from obese compared with non-obese animals; and 3) maternal obesity in humans and baboons is similar in regard to increased placental and adipose tissue macrophage infiltration, increased CD14 expression in maternal PBMC and maternal hyperleptinemia. In summary, these data demonstrate that in obese baboons in the absence of increased fetal weight, placental and fetal phenotype are consistent with those described for large-for-gestational age human fetuses.
Placenta 2009 Sep
PMID:Feto-placental adaptations to maternal obesity in the baboon. 1963 19

The diabetic pregnancy is characterized by maternal hyperglycaemia and dyslipidaemia, such that placental trophoblast cells are exposed to both. The objective was to determine the effects of hyperglycaemia, elevated non-esterified fatty acids (NEFA) and their interactions on trophoblast cell metabolism and function. Trophoblasts were isolated from normal term human placentas and established in culture for 16 h prior to experiments. Glucose utilisation, fatty acid oxidation and fatty acid esterification were determined using radiolabelled metabolic tracer methodology at various glucose and NEFA concentrations. Trophoblast lipid droplet formation including adipophilin mRNA expression, viability, apoptosis, syncytialisation, secretion of hormones and pro-inflammatory cytokines were also assessed. Glucose utilisation via glycolysis was near maximal at the low physiological glucose concentration of 4mM; whereas NEFA esterification into triacylglycerol and diacylglycerol increased linearly with increasing NEFA concentrations without evidence of plateau. Culture of trophoblasts in 0.25 mM NEFA for 24h upregulated fatty acid esterification processes, inhibited fatty acid oxidation, inhibited glycerol release (a marker of lipolysis) and promoted adipophilin and lipid droplet formation, all consistent with upregulation of fatty acid storage and buffering capacity. NEFA also promoted trophoblast syncytialisation and TNFalpha, IL-1beta, IL-6 and IL-10 production without effects on cell viability, apoptosis or hormone secretion. Hyperglycaemia caused intracellular glycogen accumulation and reduced lipid droplet formation, but had no other effects on trophoblast metabolism or function. NEFA have effects on trophoblast metabolism and function, mostly independent of glucose, that may have protective as well as pathophysiological roles in pregnancies complicated by diabetes and/or obesity.
Placenta 2010 Mar
PMID:Fatty acids alter glycerolipid metabolism and induce lipid droplet formation, syncytialisation and cytokine production in human trophoblasts with minimal glucose effect or interaction. 2008 1


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