TY - JOUR 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 DO - 10.1136/bmjdrc-2020-001586 VL - 8 IS - 2 SP - e001586 AU - Emma Assi AU - Francesca D'Addio AU - Chiara Mandò AU - Anna Maestroni AU - Cristian Loretelli AU - Moufida Ben Nasr AU - Vera Usuelli AU - Ahmed Abdelsalam AU - Andy Joe Seelam AU - Ida Pastore AU - Cinzia Magagnotti AU - Reza Abdi AU - Basset El Essawy AU - Franco Folli AU - Domenico Corradi AU - Gianvincenzo Zuccotti AU - Irene Cetin AU - Paolo Fiorina Y1 - 2020/11/01 UR - http://drc.bmj.com/content/8/2/e001586.abstract N2 - 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. ER -