RT Journal Article SR Electronic T1 Placental proteome abnormalities in women with gestational diabetes and large-for-gestational-age newborns JF BMJ Open Diabetes Research & Care JO BMJ Open Diab Res Care FD American Diabetes Association SP e001586 DO 10.1136/bmjdrc-2020-001586 VO 8 IS 2 A1 Emma Assi A1 Francesca D'Addio A1 Chiara Mandò A1 Anna Maestroni A1 Cristian Loretelli A1 Moufida Ben Nasr A1 Vera Usuelli A1 Ahmed Abdelsalam A1 Andy Joe Seelam A1 Ida Pastore A1 Cinzia Magagnotti A1 Reza Abdi A1 Basset El Essawy A1 Franco Folli A1 Domenico Corradi A1 Gianvincenzo Zuccotti A1 Irene Cetin A1 Paolo Fiorina YR 2020 UL http://drc.bmj.com/content/8/2/e001586.abstract AB 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.