scholarly journals Placental Ras Regulates Inflammation Associated with Maternal Obesity

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Stella Liong ◽  
Gillian Barker ◽  
Martha Lappas
Keyword(s):  
Protein Expression ◽  
Pregnant Women ◽  
Human Placenta ◽  
Maternal Obesity ◽  
Small Gtpase ◽  
Obese Women ◽  
Trophoblast Cells ◽  
Ras Protein ◽  
Placental Inflammation ◽  
Expression And Activity

Heightened placental inflammation and dysfunction are commonly associated in pregnant obese women compared to their pregnant lean counterparts. The small GTPase superfamily members known as the rat sarcoma viral oncogene homolog (Ras) proteins, in particular, the K-Ras and H-Ras isoforms, have been implicated to regulate inflammation. The aims were to determine the placental Ras expression and activity with maternal obesity and its role in regulating placental inflammation. Human placenta was obtained at term Caesarean section from lean and obese pregnant women to determine the effect of maternal obesity on Ras protein expression and activity. To determine the effect of Ras on inflammation induced by bacterial endotoxin LPS and proinflammatory cytokines TNF-α or IL-1β, the chemical inhibitor lonafarnib (total Ras inhibitor) and siRNA (siKRAS and siHRAS) were used. Total Ras protein expression together with combined K-Ras and H-Ras activity was significantly increased in the placenta of obese pregnant women and when stimulated with LPS, IL-1β, or TNF-α. Lonafarnib significantly suppressed LPS-, IL-1β-, or TNF-α-induced IL-6, IL-8, MCP-1, and GRO-α expression and secretion in placental tissue. Primary trophoblast cells transfected with siKRAS or siHRAS demonstrated only K-Ras silencing significantly decreased IL-1β-, TNF-α-, or LPS-induced IL-6, IL-8, and MCP-1 expression and secretion. Furthermore, siKRAS significantly reduced downstream ERK-1/2 activation induced by LPS. In trophoblast cells, ERK-1/2 signalling is required for IL-6, IL-8, MCP-1, and GRO-α secretion. These studies implicate a role for K-Ras in regulating inflammation in human placenta. Suppressing overactive placental K-Ras function may prevent adverse fetal outcomes complicated by maternal obesity.

scholarly journals Insulin Stimulates GLUT4 Trafficking to the Syncytiotrophoblast Basal Plasma Membrane in the Human Placenta

2019 ◽  
Vol 104 (9) ◽  
pp. 4225-4238 ◽  
Author(s):  
Laura B James-Allan ◽  
Jaron Arbet ◽  
Stephanie B Teal ◽  
Theresa L Powell ◽  
Thomas Jansson
Keyword(s):  
Plasma Membrane ◽  
Protein Expression ◽  
Membrane Trafficking ◽  
Human Placenta ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Maternal Obesity ◽  
Normal Body Mass Index ◽  
Basal Plasma Membrane ◽  
Basal Plasma

AbstractContextPlacental transport capacity influences fetal glucose supply. The syncytiotrophoblast is the transporting epithelium in the human placenta, expressing glucose transporters (GLUTs) and insulin receptors (IRs) in its maternal-facing microvillous plasma membrane (MVM) and fetal-facing basal plasma membrane (BM).ObjectiveThe objectives of this study were to (i) determine the expression of the insulin-sensitive GLUT4 glucose transporter and IR in the syncytiotrophoblast plasma membranes across gestation in normal pregnancy and in pregnancies complicated by maternal obesity, and (ii) assess the effect of insulin on GLUT4 plasma membrane trafficking in human placental explants.Design, Setting, and ParticipantsPlacental tissue was collected across gestation from women with normal body mass index (BMI) and mothers with obesity with appropriate for gestational age and macrosomic infants. MVM and BM were isolated.Main Outcome MeasuresProtein expression of GLUT4, GLUT1, and IR were determined by western blot.ResultsGLUT4 was exclusively expressed in the BM, and IR was predominantly expressed in the MVM, with increasing expression across gestation. BM GLUT1 expression was increased and BM GLUT4 expression was decreased in women with obesity delivering macrosomic babies. In placental villous explants, incubation with insulin stimulated Akt (S473) phosphorylation (+76%, P = 0.0003, n = 13) independent of maternal BMI and increased BM GLUT4 protein expression (+77%, P = 0.0013, n = 7) in placentas from lean women but not women with obesity.ConclusionWe propose that maternal insulin stimulates placental glucose transport by promoting GLUT4 trafficking to the BM, which may enhance glucose transfer to the fetus in response to postprandial hyperinsulinemia in women with normal BMI.

Changes in Placental Nutrient Transporter Protein Expression and Activity Across Gestation in Normal and Obese Women

2020 ◽  
Vol 27 (9) ◽  
pp. 1758-1769 ◽  
Author(s):  
Laura B. James-Allan ◽  
Stephanie Teal ◽  
Theresa L. Powell ◽  
Thomas Jansson
Keyword(s):  
Protein Expression ◽  
Obese Women ◽  
Transporter Protein ◽  
Nutrient Transporter ◽  
Expression And Activity

scholarly journals Maternal Obesity and the First Birth: A Case for Targeted Contemporary Maternity Care

2014 ◽  
Vol 4 (2) ◽  
pp. 120-129
Author(s):  
Valerie J. Slavin ◽  
Jennifer Fenwick ◽  
Jenny Gamble
Keyword(s):  
Caesarean Section ◽  
Pregnant Women ◽  
Birth Outcomes ◽  
Maternity Care ◽  
Maternal Obesity ◽  
Clinical Audit ◽  
Normal Weight ◽  
Obese Women ◽  
Model Of Care ◽  
First Birth

BACKGROUND: Obesity in childbearing women is associated with poorer pregnancy and birth outcomes, particularly caesarean section, compared with normal-weight women. The high caesarean section rate may reflect care and outcomes which occur at the time surrounding the first birth.AIM: To describe the birth outcomes of extremely obese pregnant women (body mass index [BMI] of 40 or more) experiencing their first birth.METHODS: Clinical audit was used to systematically review the care and birth outcomes of all extremely obese pregnant women experiencing their birth at one study site during a 2-year period in 2009 and 2010. Fifty participants birthed during the study period. Data were collected from booking to discharge from the maternity service and included variables such as model of care, number of appointments, and obstetric and neonatal outcomes. Descriptive statistics were used to describe and synthesize the data. Inferential statistics were used to draw inferences about the population.RESULTS: Obese women rarely had contact with a midwife, except at booking, receiving a standard model of care provided by numerous caregivers, most often inexperienced medical staff. More than half of the obese women experienced a caesarean section (56%), 2.3 times that of normal-weight primiparous women who birthed at the study site during the same period (24.2%). This was despite 64% experiencing normal pregnancy free from any complication. For women who planned to labor, birth intervention including induction of labor, augmentation for slow labor, epidural, and continuous cardiotocography was high. Caesarean occurred most often for “failure to progress” and “failed induction.”CONCLUSION: Clinical audit was useful in determining information, which suggests current maternity care provision is not meeting the needs of extremely obese women experiencing their first birth.IMPLICATIONS FOR PRACTICE: The development of effective, targeted antenatal care designed to meet the needs of extremely obese women is recommended as are strategies to keep birth normal.

The cumulative impact of parity on the body mass index (BMI) in a non-selected Lower Saxony population

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Lars Brodowski ◽  
Niels Rochow ◽  
Efrah I. Yousuf ◽  
Fabian Kohls ◽  
Constantin S. von Kaisenberg ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Pregnant Women ◽  
Body Mass ◽  
Maternal Obesity ◽  
The Body ◽  
Obese Women ◽  
Perinatal Complications ◽  
Lower Saxony ◽  
Cumulative Impact ◽  
Increased Risk

AbstractObjectivesDuring the last decade obesity has been continuously rising in adults in industrial countries. The increased occurrence of perinatal complications caused by maternal obesity poses a major challenge for obstetricians during pregnancy and childbirth. This study aims to examine the association between parity, pregnancy, birth risks, and body mass index (BMI) of women from Lower Saxony, Germany.MethodsThis retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony’s statewide quality assurance initiative. Mothers were categorized according to BMI as normal weight (18.5 to <25 kg/m2) or obese (≥30 kg/m2).ResultsMost of the mothers in this study population were either in their first (33.9%) or second pregnancy (43.4%). The mean age of women giving birth for the first time was 28.3 years. Maternal age increased with increasing parity. The proportion of pregnant women with a BMI over 30 was 11% in primiparous women, 14.3% in second para, 17.3% in third para and 24.1% in fourth para or more women. Increasing parity was positively correlated with the incidence of classical diseases related to obesity, namely diabetes mellitus, gestational diabetes, hypertension, pregnancy-related hypertension and urinary protein excretion. An increased risk of primary or secondary cesarean section was observed in the obese women, particularly during the first deliveries.ConclusionsThere is a positive and significant correlation between parity and increased maternal BMI. The highest weight gain happens during the first pregnancy. The rate of operative deliveries and complications during delivery is increased in obese pregnant women.

scholarly journals Placental function in maternal obesity

2020 ◽  
Vol 134 (8) ◽  
pp. 961-984 ◽  
Author(s):  
Amy C. Kelly ◽  
Theresa L. Powell ◽  
Thomas Jansson
Keyword(s):  
Pregnant Women ◽  
Maternal Obesity ◽  
Normal Weight ◽  
Adverse Outcomes ◽  
Obese Women ◽  
Long Term Outcomes ◽  
Placental Function ◽  
High Insulin ◽  
Short And Long Term

Abstract Maternal obesity is associated with pregnancy complications and increases the risk for the infant to develop obesity, diabetes and cardiovascular disease later in life. However, the mechanisms linking the maternal obesogenic environment to adverse short- and long-term outcomes remain poorly understood. As compared with pregnant women with normal BMI, women entering pregnancy obese have more pronounced insulin resistance, higher circulating plasma insulin, leptin, IGF-1, lipids and possibly proinflammatory cytokines and lower plasma adiponectin. Importantly, the changes in maternal levels of nutrients, growth factors and hormones in maternal obesity modulate placental function. For example, high insulin, leptin, IGF-1 and low adiponectin in obese pregnant women activate mTOR signaling in the placenta, promoting protein synthesis, mitochondrial function and nutrient transport. These changes are believed to increase fetal nutrient supply and contribute to fetal overgrowth and/or adiposity in offspring, which increases the risk to develop disease later in life. However, the majority of obese women give birth to normal weight infants and these pregnancies are also associated with activation of inflammatory signaling pathways, oxidative stress, decreased oxidative phosphorylation and lipid accumulation in the placenta. Recent bioinformatics approaches have expanded our understanding of how maternal obesity affects the placenta; however, the link between changes in placental function and adverse outcomes in obese women giving birth to normal sized infants is unclear. Interventions that specifically target placental function, such as activation of placental adiponectin receptors, may prevent the transmission of metabolic disease from obese women to the next generation.

scholarly journals Schistosome Egg Antigens Elicit a Proinflammatory Response by Trophoblast Cells of the Human Placenta

2012 ◽  
Vol 81 (3) ◽  
pp. 704-712 ◽  
Author(s):  
Emily A. McDonald ◽  
Jonathan D. Kurtis ◽  
Luz Acosta ◽  
Fusun Gundogan ◽  
Surendra Sharma ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Human Placenta ◽  
Cytokine Production ◽  
Reproductive Age ◽  
Trophoblast Cells ◽  
Proinflammatory Response ◽  
Human Trophoblast ◽  
Content Type ◽  
The Impact ◽  
Human Trophoblast Cells

ABSTRACTSchistosomiasis affects nearly 40 million women of reproductive age. Many of these women are infected while pregnant and lactating. Several studies have demonstrated transplacental trafficking of schistosome antigens; however, little is known regarding how these antigens affect the developing fetus and placenta. To evaluate the impact of schistosomiasis on trophoblasts of the human placenta, we isolated primary trophoblast cells from healthy placentas delivered at term. These trophoblasts were placed in culture and treated withSchistosoma japonicumsoluble egg antigens (SEA) or plasma fromS. japonicum-infected pregnant women. Outcomes measured included cytokine production and activation of signal transduction pathways. Treatment of primary human trophoblast cells with SEA resulted in upregulation of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8 and the chemokine macrophage inflammatory protein 1α (MIP-1α). Cytokine production in response to SEA was dose dependent and reminiscent of production in response to other proinflammatory stimuli, such as Toll-like receptor 2 (TLR2) and TLR4 agonists. In addition, the signaling pathways extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal protein kinase (JNK), p38, and NF-κB were all activated by SEA in primary trophoblasts. These effects appeared to be mediated through both carbohydrate and protein epitopes of SEA. Finally, primary trophoblasts cocultured with plasma fromS. japonicum-infected pregnant women produced increased levels of IL-8 compared to trophoblasts cocultured with plasma from uninfected pregnant women. We report here a direct impact of SEA on primary human trophoblast cells, which are critical for many aspects of a healthy pregnancy. Our data indicate that schistosome antigens can activate proinflammatory responses in trophoblasts, which might compromise maternal-fetal health in pregnancies complicated by schistosomiasis.

The Myometrium in Pregnant Women with Obesity

2020 ◽  
Vol 19 (2) ◽  
pp. 193-200
Author(s):  
Jorge A. Carvajal ◽  
Joaquín I. Oporto
Keyword(s):  
Pregnant Women ◽  
Public Health Problem ◽  
Oxytocin Receptor ◽  
High Rate ◽  
K Channel ◽  
Obese Women ◽  
Cesarean Sections ◽  
Cholesterol Levels ◽  
Myometrial Contractility ◽  
Lower Expression

: Obesity is a worldwide public health problem, affecting at least one-third of pregnant women. One of the main problems of obesity during pregnancy is the resulting high rate of cesarean section. The leading cause of this higher frequency of cesarean sections in obese women, compared with that in nonobese women, is an altered myometrial function that leads to lower frequency and potency of contractions. In this article, the disruptions of myometrial myocytes were reviewed in obese women during pregnancy that may explain the dysfunctional labor. The myometrium of obese women exhibited lower expression of connexin43, a lower function of the oxytocin receptor, and higher activity of the potassium channels. Adipokines, such as leptin, visfatin, and apelin, whose concentrations are higher in obese women, decreased myometrial contractility, perhaps by inhibiting the myometrial RhoA/ROCK pathway. The characteristically higher cholesterol levels of obese women alter myometrial myocyte cell membranes, especially the caveolae, inhibiting oxytocin receptor function, and increasing the K+ channel activity. All these changes in the myometrial cells or their environment decrease myometrial contractility, at least partially explaining the higher rate of cesarean of sections in obese women.

scholarly journals A new customised placental weight standard redefines the relationship between maternal obesity and extremes of placental size and is more closely associated with pregnancy complications than an existing population standard

2019 ◽  
Vol 11 (4) ◽  
pp. 350-359
Author(s):  
Jacqueline M. Wallace ◽  
Joeleita P. Agard ◽  
Graham W. Horgan
Keyword(s):  
Pregnancy Complications ◽  
Maternal Obesity ◽  
Population Based ◽  
Multiple Regression Model ◽  
Placental Weight ◽  
Morbidly Obese ◽  
Obese Women ◽  
Entire Cohort ◽  
Multiparous Women ◽  
The Difference

AbstractPlacental weight is a valuable indicator of its function, predicting both pregnancy outcome and lifelong health. Population-based centile charts of weight-for-gestational-age and parity are useful for identifying extremes of placental weight but fail to consider maternal size. To address this deficit, a multiple regression model was fitted to derive coefficients for predicting normal placental weight using records from healthy pregnancies of nulliparous/multiparous women of differing height and weight (n = 107,170 deliveries, 37–43 weeks gestation). The difference between actual and predicted placental weight generated a z-score/individual centile for the entire cohort including women with pregnancy complications (n = 121,591). The association between maternal BMI and placental weight extremes defined by the new customised versus population-based standard was investigated by logistic regression, as was the association between low placental weight and pregnancy complications. Underweight women had a greater risk of low placental weight [<10thcentile, OR 1.84 (95% CI 1.66, 2.05)] and obese women had a greater risk of high placental weight [>90th centile, OR 1.98 (95% CI 1.88, 2.10)] using a population standard. After customisation, the risk of high placental weight in obese/morbidly obese women was attenuated [OR 1.17 (95% CI 1.09, 1.25)]/no longer significant, while their risk of low placental weight was 59%–129% higher (P < 0.001). The customised placental weight standard was more closely associated with stillbirth, hypertensive disease, placental abruption and neonatal death than the population standard. Our customised placental weight standard reveals higher risk of relative placental growth restriction leading to lower than expected birthweights in obese women, and a stronger association between low placental weight and pregnancy complications generally. Further, it provides an alternative tool for defining placental weight extremes with implications for the placental programming of chronic disease.

scholarly journals Pregnant Women Living with Obesity: A Cross-Sectional Observational Study of Dietary Quality and Pregnancy Outcomes

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1652
Author(s):  
Margaret Charnley ◽  
Lisa Newson ◽  
Andrew Weeks ◽  
Julie Abayomi
Keyword(s):  
Pregnant Women ◽  
Maternal Obesity ◽  
Maternal Nutrition ◽  
Saturated Fatty Acids ◽  
Poor Quality ◽  
Dietary Quality ◽  
Obstetric Outcomes ◽  
Dietary Intakes ◽  
Singleton Pregnancy ◽  
Cross Sectional

Good maternal nutrition is key to optimal maternal and foetal health. A poor-quality diet is often associated with obesity, and the prevalence and severity of maternal obesity has increased significantly in recent years. This study observed dietary intakes in pregnant women living with obesity and assessed the quality of their diet. In total, 140 women with a singleton pregnancy, aged > 18 years and BMI ≥ 35 kg/m2, were recruited from antenatal clinics, weighed and completed food diaries at 16-, 28- and 36-weeks’ gestation. Clinical data were recorded directly from the women’s medical records. Nutrient intake was determined using ‘MicrodietTM’, then compared to Dietary Reference Values (DRVs). Energy intakes were comparable with DRVs, but intakes of sugar and saturated fatty acids were significantly higher. Intake of fibre and several key micronutrients (Iron, Iodine, Folate and Vitamin D) were significantly low. Several adverse obstetric outcomes were higher than the general obstetric population. Women with obesity, often considered ‘over nourished’, may have diets deficient in essential micronutrients, often associated with poor obstetric outcomes. To address the intergenerational transmission of poor health via poor diets warrants a multi-disciplinary approach focusing away from ‘dieting’ onto positive messages, emphasising key nutrients required for good maternal and foetal health.

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