PMID- 34959807 OWN - NLM STAT- MEDLINE DCOM- 20220118 LR - 20220118 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 13 IP - 12 DP - 2021 Nov 26 TI - Human Milk Oligosaccharides in Cord Blood Are Altered in Gestational Diabetes and Stimulate Feto-Placental Angiogenesis In Vitro. LID - 10.3390/nu13124257 [doi] LID - 4257 AB - (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 microg/mL) isolated from human milk, 3'-sialyllactose (3'SL, 30 microg/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. FAU - Hoch, Denise AU - Hoch D AUID- ORCID: 0000-0002-7169-7007 AD - Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria. FAU - Brandl, Waltraud AU - Brandl W AD - Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria. FAU - Strutz, Jasmin AU - Strutz J AUID- ORCID: 0000-0002-6138-7566 AD - Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria. AD - Institute of Biomedical Science, Carinthia University of Applied Science, 9020 Klagenfurt, Austria. FAU - Kofeler, Harald C AU - Kofeler HC AD - Core Facility Mass Spectrometry, Center for Medical Research, Medical University of Graz, 8010 Graz, Austria. AD - BioTechMed Graz, 8010 Graz, Austria. FAU - van Poppel, Mireille N M AU - van Poppel MNM AUID- ORCID: 0000-0001-5694-4324 AD - BioTechMed Graz, 8010 Graz, Austria. AD - Institute of Human Movement Science, Sport and Health, University of Graz, 8010 Graz, Austria. FAU - Bode, Lars AU - Bode L AD - 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. FAU - Hiden, Ursula AU - Hiden U AD - Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria. FAU - Desoye, Gernot AU - Desoye G AUID- ORCID: 0000-0002-5715-3230 AD - Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria. FAU - Jantscher-Krenn, Evelyn AU - Jantscher-Krenn E AUID- ORCID: 0000-0003-3568-891X AD - Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria. AD - BioTechMed Graz, 8010 Graz, Austria. LA - eng GR - 627056/European Commission/ GR - 16927/National Bank of Austria/ GR - KLI 784/FWF Austrian Science Fund/ PT - Journal Article DEP - 20211126 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (3'-sialyllactose) RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Oligosaccharides) RN - J2B2A4N98G (Lactose) SB - IM MH - Angiogenesis Inducing Agents/*blood MH - Cell Proliferation/drug effects MH - Chromatography, High Pressure Liquid MH - Diabetes, Gestational/*blood MH - Endothelial Cells/chemistry MH - Female MH - Fetal Blood/*chemistry MH - Humans MH - Lactose/blood MH - Milk, Human/chemistry MH - Oligosaccharides/*blood MH - Placenta/blood supply/cytology MH - Placental Circulation/*drug effects MH - Pregnancy PMC - PMC8705424 OTO - NOTNLM OT - 3'-sialyllactose OT - angiogenesis OT - cord blood OT - fibrin tube formation assay OT - gestational diabetes mellitus OT - human milk oligosaccharides OT - placenta OT - pregnancy OT - spheroid sprouting assay OT - tube formation COIS- The authors declare no conflict of interest. EDAT- 2021/12/29 06:00 MHDA- 2022/01/19 06:00 PMCR- 2021/11/26 CRDT- 2021/12/28 01:04 PHST- 2021/10/27 00:00 [received] PHST- 2021/11/23 00:00 [revised] PHST- 2021/11/24 00:00 [accepted] PHST- 2021/12/28 01:04 [entrez] PHST- 2021/12/29 06:00 [pubmed] PHST- 2022/01/19 06:00 [medline] PHST- 2021/11/26 00:00 [pmc-release] AID - nu13124257 [pii] AID - nutrients-13-04257 [pii] AID - 10.3390/nu13124257 [doi] PST - epublish SO - Nutrients. 2021 Nov 26;13(12):4257. doi: 10.3390/nu13124257.