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Increased circulating levels of Epidermal Growth Factor-like Domain 7 in pregnant women affected by preeclampsia.

ABSTRACT: Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close to term, circulating levels of EGFL7 are significantly higher in patients affected by PE when compared to normal pregnancies. Consistent with these results, villus explant cultures obtained from placentas affected by PE display increased release of EGFL7 in the culture medium when compared to those from normal placentas. Our results suggest that increased release of placenta-derived EGFL7 and increased circulating levels of EGFL7 are associated with the clinical manifestation of PE.

SUBMITTER: Massimiani M

PROVIDER: S-EPMC6486846 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Increased circulating levels of Epidermal Growth Factor-like Domain 7 in pregnant women affected by preeclampsia.

Massimiani Micol M Lacko Lauretta A LA Burke Swanson Clare S CS Salvi Silvia S Argueta Lissenya B LB Moresi Sascia S Ferrazzani Sergio S Gelber Shari E SE Baergen Rebecca N RN Toschi Nicola N Campagnolo Luisa L Stuhlmann Heidi H

Translational research : the journal of laboratory and clinical medicine 20181225

Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating l ...[more]

PMID: 30620888

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Project description:Aims/introductionMilk fat globule-epidermal growth factor 8 (MFG-E8) is the key mediator in anti-inflammatory responses that facilitate phagocytosis of apoptotic cells, and play an essential role in type 2 diabetes and pregnancy, both of which are under a low-grade inflammatory state. However, the action of MFG-E8 in gestational diabetes mellitus (GDM) is unclear. We measured plasma MFG-E8 levels in pregnancy and GDM for the first time, and elucidated possible relationships between its plasma levels and various metabolic parameters.Materials and methodsPlasma MFG-E8 levels were quantified by enzyme-linked immunosorbent assay in 66 women with GDM, 70 with normal pregnancy (p-NGT) and 44 healthy non-pregnant controls (CON), who were matched for age and body mass index. Inflammatory factors tumor necrosis factor-? (TNF-?) and C-reactive protein levels were measured, oral glucose tolerance test was carried out and ?-cell function was evaluated.ResultsPlasma MFG-E8 levels were remarkably higher in p-NGT than in CON (P = 0.024), and were further elevated in GDM vs p-NGT (P = 0.016). MFG-E8 concentrations correlated positively with hemoglobin A1c, glucose levels and insulin resistance (homeostasis model assessment for insulin resistance), and correlated inversely with TNF-? and insulin secretion evaluated by disposition indices in pregnancies. Fasting glucose levels, disposition index of first phase insulin secretion and TNF-? were independent predictors of MFG-E8 levels in pregnancies. Logistic regression analyses showed that women in the third tertile of MFG-E8 levels had a markedly elevated risk of GDM.ConclusionsCirculating MFG-E8 levels are dramatically elevated in pregnancy, and are significantly higher in GDM vs p-NGT. MFG-E8 concentrations are significantly associated with TNF-?, fasting glucose levels, homeostasis model assessment for insulin resistance and disposition indices. However, further studies are required to elucidate the regulation mechanism of MFG-E8 during pregnancy and GDM.

Project description:The purpose of this study was to determine the effect of exercise during pregnancy in sedentary women with obesity on longitudinal changes in long-chain acylcarnitine (LC-AC) concentrations. We hypothesized that exercise training would significantly decrease circulating LC-ACs throughout gestation compared with a nonexercise control group. Pregnant women with obesity considered otherwise healthy [n = 80, means ± SD; body mass index (BMI): 36.9 ± 5.7 kg/m2] were randomized into an exercise (n = 40, aerobic/resistance 3 times/wk, ∼13th gestation week until birth) or a nonexercise control (n = 40) group. At gestation week 12.2 ± 0.5 and 36.0 ± 0.4, a submaximal exercise test was conducted, and indirect calorimetry was used to measure relative resting energy expenditure (REE), as well as respiratory exchange ratio (RER) at rest. Fasting blood samples were collected and analyzed for LC-AC concentrations. Fitness improved with prenatal exercise training; however, exercise training did not affect circulating LC-AC. When groups were collapsed, LC-ACs decreased during gestation (combined groups, P < 0.001), whereas REE (kcal/kg/day, P = 0.008) increased. However, average REE relative to fat-free mass (FFM) (kcal/kg FFM/day) and RER did not change. There was an inverse relationship between the change in RER and all LC-ACs (except C18:2) throughout gestation (C14: r = -0.26, P = 0.04; C16: r = -0.27, P = 0.03; C18:1: r = -0.28, P = 0.02). In summary, a moderate-intensity exercise intervention during pregnancy in women with obesity did not alter LC-ACs concentrations versus control, indicating that the balance between long-chain fatty acid availability and oxidation neither improved nor worsened with an exercise intervention.NEW & NOTEWORTHY This research showed that a moderate-intensity prenatal exercise program, consisting of aerobic and resistance training, did not negatively impact normal alterations in substrate supply and demand for the mother and the offspring throughout gestation. Findings provide support for metabolic safety of exercise during pregnancy.

Dataset Information

Increased circulating levels of Epidermal Growth Factor-like Domain 7 in pregnant women affected by preeclampsia.

Publications

Increased circulating levels of Epidermal Growth Factor-like Domain 7 in pregnant women affected by preeclampsia.

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