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Article

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

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Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria
2
Institute of Biomedical Science, Carinthia University of Applied Science, 9020 Klagenfurt, Austria
3
Core Facility Mass Spectrometry, Center for Medical Research, Medical University of Graz, 8010 Graz, Austria
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BioTechMed Graz, 8010 Graz, Austria
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Institute of Human Movement Science, Sport and Health, University of Graz, 8010 Graz, Austria
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Department 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, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Michael Freemark
Nutrients 2021, 13(12), 4257; https://doi.org/10.3390/nu13124257
Received: 27 October 2021 / Revised: 23 November 2021 / Accepted: 24 November 2021 / Published: 26 November 2021
(This article belongs to the Section Nutrition in Women)
(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, n = 25) or GDM (n = 26). We investigated in vitro angiogenesis using primary feto-placental endothelial cells (fpECs) from term placentas after healthy pregnancy (n = 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% (p < 0.05), in spheroid assays, by 32% (p < 0.05) and 21% (p = 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. View Full-Text
Keywords: pregnancy; gestational diabetes mellitus; human milk oligosaccharides; angiogenesis; cord blood; 3′-sialyllactose; placenta; tube formation; spheroid sprouting assay; fibrin tube formation assay pregnancy; gestational diabetes mellitus; human milk oligosaccharides; angiogenesis; cord blood; 3′-sialyllactose; placenta; tube formation; spheroid sprouting assay; fibrin tube formation assay
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MDPI and ACS Style

Hoch, D.; Brandl, W.; Strutz, J.; Köfeler, H.C.; van Poppel, M.N.M.; Bode, L.; Hiden, U.; Desoye, G.; Jantscher-Krenn, E. Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro. Nutrients 2021, 13, 4257. https://doi.org/10.3390/nu13124257

AMA Style

Hoch D, Brandl W, Strutz J, Köfeler HC, van Poppel MNM, Bode L, Hiden U, Desoye G, Jantscher-Krenn E. Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro. Nutrients. 2021; 13(12):4257. https://doi.org/10.3390/nu13124257

Chicago/Turabian Style

Hoch, Denise, Waltraud Brandl, Jasmin Strutz, Harald C. Köfeler, Mireille N. M. van Poppel, Lars Bode, Ursula Hiden, Gernot Desoye, and Evelyn Jantscher-Krenn. 2021. "Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro" Nutrients 13, no. 12: 4257. https://doi.org/10.3390/nu13124257

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