Gestational diabetes mellitus affects placental iron homeostasis: Mechanism and clinical implications.

Zaugg, Jonas; Melhem, Hassan; Huang, Xiao; Wegner, Malgorzata; Baumann, Marc; Surbek, Daniel; Körner, Meike; Albrecht, Christiane (2020). Gestational diabetes mellitus affects placental iron homeostasis: Mechanism and clinical implications. FASEB journal, 34(6), pp. 7311-7329. Federation of American Societies for Experimental Biology 10.1096/fj.201903054R

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Clinical studies suggest that pregnant women with elevated iron levels are more vulnerable to develop gestational diabetes mellitus (GDM), but the causes and underlying mechanisms are unknown. We hypothesized that hyperglycemia induces cellular stress responses leading to dysregulated placental iron homeostasis. Hence, we compared the expression of genes/proteins involved in iron homeostasis in placentae from GDM and healthy pregnancies (n = 11 each). RT-qPCR and LC-MS/MS analyses revealed differential regulation of iron transporters/receptors (DMT1/FPN1/ZIP8/TfR1), iron sensors (IRP1), iron regulators (HEPC), and iron oxidoreductases (HEPH/Zp). To identify the underlying mechanisms, we adapted BeWo trophoblast cells to normoglycemic (N), hyperglycemic (H), and hyperglycemic-hyperlipidemic (HL) conditions and assessed Fe3+ -uptake, expression patterns, and cellular pathways involving oxidative stress (OS), ER-stress, and autophagy. H and HL induced alterations in cellular morphology, differential iron transporter expression, and reduced Fe3+ -uptake confirming the impact of hyperglycemia on iron transport observed in GDM patients. Pathway analysis and rescue experiments indicated that dysregulated OS and disturbed autophagy processes contribute to the reduced placental iron transport under hyperglycemic conditions. These adaptations could represent a protective mechanism preventing the oxidative damage for both fetus and placenta caused by highly oxidative iron. In pregnancies with risk for GDM, antioxidant treatment, and controlled iron supplementation could help to balance placental OS levels protecting mother and fetus from impaired iron homeostasis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Faculty Institutions > NCCR TransCure
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Zaugg, Jonas; Melhem, Hassan; Huang, Xiao; Wegner, Malgorzata; Baumann, Marc; Surbek, Daniel; Körner Jachertz, Meike and Albrecht, Christiane

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0892-6638

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

27 May 2020 13:40

Last Modified:

18 Jun 2020 01:33

Publisher DOI:

10.1096/fj.201903054R

PubMed ID:

32285992

Uncontrolled Keywords:

DMT1 ZIP8 antioxidant treatment autophagy ferroportin immunohistochemistry iron uptake oxidative stress placenta transferrin receptor trophoblast cells

BORIS DOI:

10.7892/boris.144148

URI:

https://boris.unibe.ch/id/eprint/144148

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