Placental proteome abnormalities in women with gestational diabetes and large-for-gestational-age newborns

Emma Assi, Francesca D'Addio, Chiara Mandò, Anna Maestroni, Cristian Loretelli, Moufida Ben Nasr, Vera Usuelli, Ahmed Abdelsalam, Andy Joe Seelam, Ida Pastore, Cinzia Magagnotti, Reza Abdi, Basset El Essawy, Franco Folli, Domenico Corradi, Gianvincenzo Zuccotti, Irene Cetin, Paolo Fiorina

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy and is associated with development of short-term and long-term complications for newborns, with large-for-gestational-age (LGA) being particularly common. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood. Research design and methods A proteomic approach was used to analyze placental samples obtained from healthy pregnant women (n=5), patients with GDM (n=12) and with GDM and LGA (n=5). Effects of altered proteins on fetal development were tested in vitro in human embryonic stem cells (hESCs). Results Here, we demonstrate that the placental proteome is altered in pregnant women affected by GDM with LGA, with at least 37 proteins differentially expressed to a higher degree (p<0.05) as compared with those with GDM but without LGA. Among these proteins, 10 are involved in regulating tissue differentiation and/or fetal growth and development, with bone marrow proteoglycan (PRG2) and dipeptidyl peptidase-4 (DPP-4) being highly expressed. Both PRG2 and DPP-4 altered the transcriptome profile of stem cells differentiation markers when tested in vitro in hESCs, suggesting a potential role in the onset of fetal abnormalities. Conclusions Our findings suggest that placental dysfunction may be directly responsible for abnormal fetal growth/development during GDM. Once established on a larger population, inhibitors of the pathways involving those altered factors may be tested in conditions such as GDM and LGA, in which therapeutic approaches are still lacking.

Original languageEnglish
Article numbere001586
JournalBMJ Open Diabetes Research and Care
Volume8
Issue number2
DOIs
Publication statusPublished - Nov 13 2020

Keywords

  • diabetes
  • gestational
  • placenta
  • proteomics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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