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5. Fluid shear stress induces a shift from glycolytic to amino acid pathway in human trophoblasts

Author

Brugger, Beatrice Anna, Neuper, Lena, Guettler, Jacqueline, Forstner, Désirée, Wernitznig, Stefan, Kummer, Daniel, Lyssy, Freya, Feichtinger, Julia, Krappinger, Julian, El-Heliebi, Amin, Bonstingl, Lilli, Moser, Gerit, Rodriguez-Blanco, Giovanny, Bachkönig, Olaf A., Gottschalk, Benjamin, Gruber, Michael, Nonn, Olivia, Herse, Florian, Verlohren, Stefan, Frank, Hans-Georg, Barapatre, Nirav, Kampfer, Cornelia, Fluhr, Herbert, Desoye, Gernot, and Gauster, Martin

Published
2023
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11. Maternal Diabetes and Obesity

Author

Dahlstrom, Jane Esther, Nolan, Christopher James, Desoye, Gernot, Baergen, Rebecca N., editor, Burton, Graham J., editor, and Kaplan, Cynthia G., editor

Published
2022
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12. The RhoA guanine exchange factor ABR: a glucose‐sensitive mediator of actin reorganization in feto‐placental arterial endothelial cells altered by gestational diabetes mellitus

Author

Tokic, Silvija, primary, Novakovic, Boris, additional, Leopold‐Posch, Barbara, additional, Mühlberger, Magdalena, additional, Hoch, Denise, additional, Lögl, Jelena, additional, Bernhart, Eva M., additional, Saffery, Richard, additional, Desoye, Gernot, additional, and Hiden, Ursula, additional

Published
2024
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15. MCM proteins are up-regulated in placentas of women with reduced insulin sensitivity.

Author

Bandres-Meriz, Julia, Sanz-Cuadrado, Marta Inmaculada, de Mendoza, Irene Hurtado, Majali-Martinez, Alejandro, Honeder, Sophie Elisabeth, Cindrova-Davies, Tereza, Birner-Gruenberger, Ruth, Dalgaard, Louise Torp, and Desoye, Gernot

Abstract

In the first trimester of pregnancy the human placenta grows rapidly, making it sensitive to changes in the intrauterine environment. To test whether exposure to an environment in utero often associated with obesity modifies placental proteome and function, we performed un- targeted proteomics (LC-MS/MS) in placentas from 19 women (gestational age 35-48 days, i.e. 5+0-6+6 weeks). Maternal clinical traits (body mass index, leptin, glucose, C-peptide and insulin sensitivity) and gestational age were recorded. DNA replication and cell cycle pathways were enriched in the proteome of placentas of women with low maternal insulin sensitivity. Driving these pathways were the minichromosome maintenance (MCM) proteins MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7 (MCM-complex). These proteins are part of the pre-replicative complex and participate in DNA damage repair. Indeed, MCM6 and γH2AX (DNA-damage marker) protein levels correlated in first trimester placental tissue (r = 0.514, P<0.01). MCM6and γH2AX co-localized to nuclei of villous cytotrophoblast cells, the proliferative cell type of the placenta, suggesting increased DNA damage in this cell type. To mimic key features of the intrauterine obesogenic environment, a first trimester trophoblast cell line, i.e., ACH-3P, was exposed to high insulin (10 nM) or low oxygen tension (2.5% O2). There was a significant correlation between MCM6 and γH2AX protein levels, but these were independent of insulin or oxygen exposure. These findings show that chronic exposure in utero to reduced maternal insulin sensitivity during early pregnancy induces changes in the early first trimester placental proteome. Pathways related to DNA replication, cell cycle and DNA damage repair appear especially sensitive to such an in utero environment. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Less sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women—a secondary analysis of the DALI study

Author

Dieberger, Anna M., Desoye, Gernot, Stolz, Erwin, Hill, David J., Corcoy, Rosa, Simmons, David, Harreiter, Jürgen, Kautzky-Willer, Alexandra, Dunne, Fidelma, Devlieger, Roland, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Lapolla, Annunziata, Dalfra, Maria Grazia, Bertolotto, Alessandra, Galjaard, Sander, Adelantado, Juan M., Jensen, Dorte Møller, Andersen, Lise-Lotte, Tanvig, Mette, Damm, Peter, Mathiesen, Elisabeth Reinhardt, Snoek, Frank J., Jelsma, Judith G. M., and van Poppel, Mireille N. M.

Published
2021
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20. Placental structural adaptation to maternal physical activity and sedentary behavior: findings of the DALI lifestyle study.

Author

Zafaranieh, Saghi, Siwetz, Monika, Leopold-Posch, Barbara, Kummer, Daniel, Huppertz, Berthold, Desoye, Gernot, Poppel, Mireille van, and Group, DALI Core Investigator

Subjects
SEDENTARY behavior, PHYSICAL activity, PLACENTA, OBESITY in women, PREGNANT women, PRENATAL bonding, COMPULSIVE eating
Abstract

STUDY QUESTION Are maternal levels of moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) in obese pregnant women associated with placental structural adaptations for facilitating oxygen delivery to the fetus? SUMMARY ANSWER Higher maternal MVPA and ST are associated with a higher density of villi, a proxy measure of placental surface area for oxygen delivery to the fetus, without further added placental vessels. WHAT IS KNOWN ALREADY Physical activity during pregnancy intermittently reduces uterine blood flow, potentially limiting placental and fetal oxygen supply. The placenta can mount several adaptive responses, including enlargement of the surface area of villi and/or feto-placental vessels to accommodate fetal needs. Early research on the morphology and growth of the placenta with exercise interventions has shown inconsistencies and is lacking, particularly in non-lean pregnant women. STUDY DESIGN, SIZE, DURATION This study is a secondary longitudinal analysis of the vitamin D and lifestyle intervention for gestational diabetes prevention (DALI) randomized controlled trial. The prospective study was conducted between 2012 and 2015 in nine European countries at 11 different sites. In this analysis, 92 pregnant women with a BMI ≥ 29 kg/m2 were combined into one cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS MVPA and percentage of time spent sedentary (% ST) were measured with accelerometers during gestation. Placental sections were immunostained for endothelial cell-specific CD34. Artificial intelligence (AI)-based stereology assessed villous density, number, and cross-sectional area of vessels on whole-slide images and in selected regions comprising peripheral villi only, where the majority of vascular adaptations occur. Expression of pro- and anti-angiogenic factors was quantified using molecular counting analysis. MAIN RESULTS AND THE ROLE OF CHANCE In multivariable regression, higher levels of maternal MVPA (min/day) were associated with a higher density of villi in both whole-slide images (beta 0.12; 95% CI 0.05, 0.2) and selected regions (0.17; CI 0.07, 0.26). Unexpectedly, ST was also positively associated with density of villi (0.23; CI 0.04, 0.43). MVPA and ST were not associated with vessel count/mm2 villous area, vessel area, or pro- and anti-angiogenic factor mRNA expression. All estimates and statistical significance of the sensitivity analyses excluding smokers, women who developed gestational diabetes or pre-eclampsia and/or pregnancy-induced hypertension were similar in the main analysis. LIMITATIONS, REASONS FOR CAUTION The placenta is a complex organ undergoing dynamic changes. While various adjustments were made to account for different maternal contributing factors, in addition to the outcome measures, various other factors could impact oxygen delivery to the fetus. WIDER IMPLICATIONS OF THE FINDINGS For the first time, we evaluated the association between placental structures quantified using an AI-based approach with objectively measured physical activity and ST at multiple time points in pregnant women with obesity. The observed adaptations contribute to the advancement of our understanding of the hemodynamics and adaptations of the placental unit in response to MVPA and ST. However, our results might not be generalizable to lean pregnant women. STUDY FUNDING/COMPETING INTEREST(S) The DALI project has received funding from the European Community's 7th Framework Program (FP7/2007–2013) under grant agreement no. 242187. The funders had no role in study design, collection of data, analyses, writing of the article, or the decision to submit it for publication. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER ISRCTN70595832. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Performance of early pregnancy HbA1c for predicting gestational diabetes mellitus and adverse pregnancy outcomes in obese European women

Author

Immanuel, Jincy, Simmons, David, Desoye, Gernot, Corcoy, Rosa, Adelantado, Juan M., Devlieger, Roland, Lapolla, Annunziata, Dalfra, Maria G., Bertolotto, Alessandra, Harreiter, Jürgen, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Dunne, Fidelma P., Damm, Peter, Mathiesen, Elisabeth R., Jensen, Dorte M., Andersen, Lise Lotte T., Hill, David J., Jelsma, Judith G.M., Snoek, Frank J., Scharnagl, Hubert, Galjaard, Sander, Kautzky-Willer, Alexandra, and VAN Poppel, Mireille N.M.

Published
2020
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29. Human Milk Oligosaccharides in Maternal Serum Respond to Oral Glucose Load and Are Associated with Insulin Sensitivity

Author

Weiser-Fuchs, Marie-Therese, primary, Maggauer, Elena, additional, van Poppel, Mireille N. M., additional, Csapo, Bence, additional, Desoye, Gernot, additional, Köfeler, Harald C., additional, Groselj-Strele, Andrea, additional, Trajanoski, Slave, additional, Fluhr, Herbert, additional, Obermayer-Pietsch, Barbara, additional, and Jantscher-Krenn, Evelyn, additional

Published
2023
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30. Methylation of serotonin regulating genes in cord blood cells: modulation by maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

Author

Bečeheli, Ivona, primary, Horvatiček, Marina, additional, Perić, Maja, additional, Nikolić, Barbara, additional, Holuka, Cyrielle, additional, Klasić, Marija, additional, Ivanišević, Marina, additional, Starčević, Mirta, additional, Desoye, Gernot, additional, Hranilović, Dubravka, additional, Turner, Jonathan D., additional, and Štefulj, Jasminka, additional

Published
2023
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36. Maternal Angiotensin Increases Placental Leptin in Early Gestation via an Alternative Renin-Angiotensin System Pathway: Suggesting a Link to Preeclampsia

Author

Nonn, Olivia, Fischer, Cornelius, Geisberger, Sabrina, El-Heliebi, Amin, Kroneis, Thomas, Forstner, Désirée, Desoye, Gernot, Staff, Anne Cathrine, Sugulle, Meryam, Dechend, Ralf, Pecks, Ulrich, Kollmann, Martina, Stern, Christina, Cartwright, Judith E., Whitley, Guy S., Thilaganathan, Basky, Wadsack, Christian, Huppertz, Berthold, Herse, Florian, and Gauster, Martin

Published
2021
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37. A reduction in sedentary behaviour in obese women during pregnancy reduces neonatal adiposity: the DALI randomised controlled trial

Author

van Poppel, Mireille N. M., Simmons, David, Devlieger, Roland, van Assche, F. Andre, Jans, Goele, Galjaard, Sander, Corcoy, Rosa, Adelantado, Juan M., Dunne, Fidelma, Harreiter, Jürgen, Kautzky-Willer, Alexandra, Damm, Peter, Mathiesen, Elisabeth R., Jensen, Dorte M., Andersen, Lise-Lotte, Tanvig, Mette, Lapolla, Annunziata, Dalfra, Maria G., Bertolotto, Alessandra, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Hill, David, Snoek, Frank J., Jelsma, Judith G. M., and Desoye, Gernot

Published
2019
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43. Correction to: The Effects of Lifestyle and/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have we Learned from the DALI Studies?

Author

Harreiter, Jürgen, Desoye, Gernot, van Poppel, Mireille N. M., Kautzky-Willer, Alexandra, Dunne, Fidelma, Corcoy, Rosa, Devlieger, Roland, Simmons, David, Adelantado, Juan M., Damm, Peter, Mathiesen, Elizabeth Reinhardt, Jensen, Dorte Moeller, Anderson, Lise Lotte T., Lapolla, Annunziata, Dalfrà, Maria G., Bertolotto, Alessandra, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Hill, David J., and Snoek, Frank J.

Published
2020
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44. The Effects of Lifestyle and/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have We Learned from the DALI Studies?

Author

Harreiter, Jürgen, Desoye, Gernot, van Poppel, Mireille N. M., Kautzky-Willer, Alexandra, Dunne, Fidelma, Corcoy, Rosa, Devlieger, Roland, Simmons, David, Adelantado, Juan M., Damm, Peter, Mathiesen, Elizabeth Reinhardt, Jensen, Dorte Moeller, Anderson, Lise Lotte T., Lapolla, Annunziata, Dalfrà, Maria G., Bertolotto, Alessandra, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Hill, David J., and Snoek, Frank J.

Published
2019
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45. The Role of Early Pregnancy Maternal pGCD59 Levels in Predicting Neonatal Hypoglycemia—Subanalysis of the DALI Study

Author

Bogdanet, Delia, Luque-Fernandez, Miguel Angel, Toth-Castillo, Michelle, Desoye, Gernot, O'Shea, Paula M, Dunne, Fidelma P, Halperin, Jose, A, Lapolla, A, and DALI Core Investigator Group

Subjects
Blood Glucose, Glycation, Epidemiology, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Infant, Newborn, Infant, Glucose Tolerance Test, Biochemistry, Hypoglycemia, Infant, Newborn, Diseases, Biomarkers, Neonatal hypoglycaemia, Prediction, Diabetes, Gestational, Fetal Diseases, Endocrinology, Pregnancy, Humans, Female
Abstract

Context Neonatal hypoglycaemia (NH) is the most common metabolic problem in infants born of mothers with gestational diabetes. Plasma glycated CD59 (pGCD59) is an emerging biomarker that has shown potential in identifying women at risk of developing gestational diabetes. The aim of this study was to assess the association between early maternal levels of pGCD59 and NH. Objective The aim of this study was to assess the association between early pregnancy maternal levels of plasma glycated CD59 (pGCD59) and neonatal hypoglycemia (NH). Methods This is an observational study of pregnant women with a prepregnancy body mass index (BMI) greater than or equal to 29 screened for eligibility to participate in the Vitamin D and Lifestyle Intervention for Gestational Diabetes (DALI) trial. This analysis included 399 pregnancies. Levels of pGCD59 were measured in fasting maternal samples taken at the time of a 75-g, 2-hour oral glucose tolerance test performed in early pregnancy ( Results We identified 30 infants with NH. Maternal levels of pGCD59 in early pregnancy were positively associated with the prevalence of NH (one-way analysis of variance, P Conclusion Although pGCD59 levels in early pregnancy in women with BMI greater than or equal to 29 are associated with NH, our results indicate that this biomarker by itself is only a fair predictor of NH.

Published
2022

49. Gestational Hypertension and High-Density Lipoprotein Function:An Explorative Study in Overweight/Obese Women of the DALI Cohort

Author

Stadler, Julia T., van Poppel, M. N. M., Christoffersen, Christina, Hill, David, Wadsack, Christian, Simmons, David, Desoye, Gernot, Marsche, Gunther, DALI Core Investigator Grp, Stadler, Julia T., van Poppel, M. N. M., Christoffersen, Christina, Hill, David, Wadsack, Christian, Simmons, David, Desoye, Gernot, Marsche, Gunther, and DALI Core Investigator Grp

Abstract

Gestational hypertension (GHTN) is associated with an increased cardiovascular risk for mothers and their offspring later in life. High-density lipoproteins (HDL) are anti-atherogenic by promoting efflux of cholesterol from macrophages and suppression of endothelial cell activation. Functional impairment of HDL in GHTN-complicated pregnancies may affect long-term health of both mothers and offspring. We studied functional parameters of maternal and neonatal HDL in 192 obese women (pre-pregnancy BMI >= 29), who were at high risk for GHTN. Maternal blood samples were collected longitudinally at

Published
2023

50. Secular trend for increasing birthweight in offspring of pregnant women with type 1 diabetes:is improved placentation the reason?

Author

Desoye, Gernot, Ringholm, Lene, Damm, Peter, Mathiesen, Elisabeth R., van Poppel, Mireille N. M., Desoye, Gernot, Ringholm, Lene, Damm, Peter, Mathiesen, Elisabeth R., and van Poppel, Mireille N. M.

Abstract

Despite enormous progress in managing blood glucose levels, pregnancy in women with type 1 diabetes still carries risks for the growing fetus. While, previously, fetal undergrowth was not uncommon in these women, with improved maternal glycaemic control we now see an increased prevalence of fetal overgrowth. Besides short-term implications, offspring of women with type 1 diabetes are more likely to become obese and to develop diabetes and features of the metabolic syndrome. Here, we argue that the increase in birthweight is paradoxically related to improved glycaemic control in the pre- and periconceptional periods. Good glycaemic control reduces the prevalence of microangiopathy and improves placentation in early pregnancy, which may lead to unimpeded fetal nutrition. Even mild maternal hyperglycaemia may then later result in fetal overnutrition. This notion is supported by circumstantial evidence that lower HbA1c levels as well as increases in markers of placental size and function in early pregnancy are associated with large-for-gestational age neonates. We also emphasise that neonates with normal birthweight can have excessive fat deposition. This may occur when poor placentation leads to initial fetal undergrowth, followed by fetal overnutrition due to maternal hyperglycaemia. Thus, the complex interaction of glucose levels during different periods of pregnancy ultimately determines the risk of adiposity, which can occur in fetuses with both normal and elevated birthweight. Prevention of fetal adiposity calls for revised goal setting to enable pregnant women to maintain blood glucose levels that are closer to normal. This could be supported by continuous glucose monitoring throughout pregnancy and appropriate maternal gestational weight gain. Future research should consider the measurement of adiposity in neonates. Graphical abstract: [Figure not available: see fulltext.].

Published
2023

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