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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

(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.

Details

Title
Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro
Author
Hoch, Denise 1   VIAFID ORCID Logo  ; Brandl, Waltraud 1 ; Strutz, Jasmin 2   VIAFID ORCID Logo  ; Köfeler, Harald C 3 ; Mireille N M van Poppel 4   VIAFID ORCID Logo  ; Bode, Lars 5 ; Hiden, Ursula 1 ; Desoye, Gernot 1   VIAFID ORCID Logo  ; Jantscher-Krenn, Evelyn 6   VIAFID ORCID Logo 

 Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria; [email protected] (D.H.); [email protected] (W.B.); [email protected] (J.S.); [email protected] (G.D.) 
 Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria; [email protected] (D.H.); [email protected] (W.B.); [email protected] (J.S.); [email protected] (G.D.); Institute of Biomedical Science, Carinthia University of Applied Science, 9020 Klagenfurt, Austria 
 Core Facility Mass Spectrometry, Center for Medical Research, Medical University of Graz, 8010 Graz, Austria; [email protected]; BioTechMed Graz, 8010 Graz, Austria; [email protected] 
 BioTechMed Graz, 8010 Graz, Austria; [email protected]; Institute of Human Movement Science, Sport and Health, University of Graz, 8010 Graz, Austria 
 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; [email protected] 
 Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria; [email protected] (D.H.); [email protected] (W.B.); [email protected] (J.S.); [email protected] (G.D.); BioTechMed Graz, 8010 Graz, Austria; [email protected] 
First page
4257
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
20726643
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2612820782
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.