Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro

(1) Background: Human milk oligosaccharides (HMOs) are present in maternal serum during pregnancy and their composition is altered in gestational diabetes (GDM). HMOs are also in fetal cord blood and in contact with the feto-placental endothelium, potentially affecting its functions, such as angioge...

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Main Authors: Denise Hoch, Waltraud Brandl, Jasmin Strutz, Harald C. Köfeler, Mireille N. M. van Poppel, Lars Bode, Ursula Hiden, Gernot Desoye, Evelyn Jantscher-Krenn
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/13/12/4257
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author Denise Hoch
Waltraud Brandl
Jasmin Strutz
Harald C. Köfeler
Mireille N. M. van Poppel
Lars Bode
Ursula Hiden
Gernot Desoye
Evelyn Jantscher-Krenn
author_facet Denise Hoch
Waltraud Brandl
Jasmin Strutz
Harald C. Köfeler
Mireille N. M. van Poppel
Lars Bode
Ursula Hiden
Gernot Desoye
Evelyn Jantscher-Krenn
author_sort Denise Hoch
collection DOAJ
description (1) Background: Human milk oligosaccharides (HMOs) are present in maternal serum during pregnancy and their composition is altered in gestational diabetes (GDM). HMOs are also in fetal cord blood and in contact with the feto-placental endothelium, potentially affecting its functions, such as angiogenesis. We hypothesized that cord blood HMOs are changed in GDM and contribute to increased feto-placental angiogenesis, hallmark of GDM. (2) Methods: Using HPLC, we quantified HMOs in cord blood of women with normal glucose tolerance (NGT, <i>n</i> = 25) or GDM (<i>n</i> = 26). We investigated in vitro angiogenesis using primary feto-placental endothelial cells (fpECs) from term placentas after healthy pregnancy (<i>n</i> = 10), in presence or absence of HMOs (100 µg/mL) isolated from human milk, 3′-sialyllactose (3′SL, 30 µg/mL) and lactose (glycan control) and determined network formation (Matrigel assay), proliferation (MTT assays), actin organization (F-actin staining), tube formation (fibrin tube formation assay) and sprouting (spheroid sprouting assay). (3) Results: 3′SL was higher in GDM cord blood. HMOs increased network formation, HMOs and 3’SL increased proliferation and F-actin staining. In fibrin assays, HMOs and 3’SL increased total tube length by 24% and 25% (<i>p</i> < 0.05), in spheroid assays, by 32% (<i>p</i> < 0.05) and 21% (<i>p</i> = 0.056), respectively. Lactose had no effect. (4) Conclusions: Our study suggests a novel role of HMOs in feto-placental angiogenesis and indicates a contribution of HMO composition to altered feto-placental vascularization in GDM.
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spelling doaj.art-0f7060beb87a4b03b49110807c10ed2e2023-11-23T09:55:09ZengMDPI AGNutrients2072-66432021-11-011312425710.3390/nu13124257Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In VitroDenise Hoch0Waltraud Brandl1Jasmin Strutz2Harald C. Köfeler3Mireille N. M. van Poppel4Lars Bode5Ursula Hiden6Gernot Desoye7Evelyn Jantscher-Krenn8Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, AustriaDepartment of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, AustriaDepartment of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, AustriaCore Facility Mass Spectrometry, Center for Medical Research, Medical University of Graz, 8010 Graz, AustriaBioTechMed Graz, 8010 Graz, AustriaDepartment of Pediatrics and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (LRF MoMI CoRE), University of California San Diego, La Jolla, CA 92093, USADepartment of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, AustriaDepartment of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, AustriaDepartment of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria(1) Background: Human milk oligosaccharides (HMOs) are present in maternal serum during pregnancy and their composition is altered in gestational diabetes (GDM). HMOs are also in fetal cord blood and in contact with the feto-placental endothelium, potentially affecting its functions, such as angiogenesis. We hypothesized that cord blood HMOs are changed in GDM and contribute to increased feto-placental angiogenesis, hallmark of GDM. (2) Methods: Using HPLC, we quantified HMOs in cord blood of women with normal glucose tolerance (NGT, <i>n</i> = 25) or GDM (<i>n</i> = 26). We investigated in vitro angiogenesis using primary feto-placental endothelial cells (fpECs) from term placentas after healthy pregnancy (<i>n</i> = 10), in presence or absence of HMOs (100 µg/mL) isolated from human milk, 3′-sialyllactose (3′SL, 30 µg/mL) and lactose (glycan control) and determined network formation (Matrigel assay), proliferation (MTT assays), actin organization (F-actin staining), tube formation (fibrin tube formation assay) and sprouting (spheroid sprouting assay). (3) Results: 3′SL was higher in GDM cord blood. HMOs increased network formation, HMOs and 3’SL increased proliferation and F-actin staining. In fibrin assays, HMOs and 3’SL increased total tube length by 24% and 25% (<i>p</i> < 0.05), in spheroid assays, by 32% (<i>p</i> < 0.05) and 21% (<i>p</i> = 0.056), respectively. Lactose had no effect. (4) Conclusions: Our study suggests a novel role of HMOs in feto-placental angiogenesis and indicates a contribution of HMO composition to altered feto-placental vascularization in GDM.https://www.mdpi.com/2072-6643/13/12/4257pregnancygestational diabetes mellitushuman milk oligosaccharidesangiogenesiscord blood3′-sialyllactose
spellingShingle Denise Hoch
Waltraud Brandl
Jasmin Strutz
Harald C. Köfeler
Mireille N. M. van Poppel
Lars Bode
Ursula Hiden
Gernot Desoye
Evelyn Jantscher-Krenn
Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro
Nutrients
pregnancy
gestational diabetes mellitus
human milk oligosaccharides
angiogenesis
cord blood
3′-sialyllactose
title Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro
title_full Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro
title_fullStr Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro
title_full_unstemmed Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro
title_short Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro
title_sort human milk oligosaccharides in cord blood are altered in gestational diabetes and stimulate feto placental angiogenesis in vitro
topic pregnancy
gestational diabetes mellitus
human milk oligosaccharides
angiogenesis
cord blood
3′-sialyllactose
url https://www.mdpi.com/2072-6643/13/12/4257
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