Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy, affecting 3% to 25% women, and it is associated with abnormal fetal growth. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood. In order to discover novel factors that may play a role in placental function and fetal development, we interrogated the placental proteomes of healthy (CTRL, n=5) and GDM-affected (n=5) pregnant women using an unbiased proteomic approach. We demonstrated that the placental proteome is altered in GDM, with at least 64 proteins differentially expressed to a high degree (p<0.001) in GDM as compared to CTRL. Among those, 10 proteins are strictly involved in the mother-to-fetus crosstalk. While some of these proteins (e.g., C5, KRT8 and ATPSB) primarily exert protective effects of the trophoblast both in structure and function (e.g., invasion, angiogenesis, oxidative stress, barrier, energy support), others (e.g., CPAN6, TFRC and EZR) were importantly involved in fetal development (iron, muscle differentiation, nutrients) and protection from fetal loss (anticoagulant, regulation of epithelial-to-mesenchymal transition). These alterations in the GDM placental proteome suggest that placental dysfunction may be directly responsible for abnormal fetal growth/development during GDM. Targeting these proteins may thus offer therapeutic potentials for managing and treating GDM.
E. Assi: None. F. D'Addio: None. M. Ben Nasr: None. C. Loretelli: None. A. Maestroni: None. V. Usuelli: None. C. Mandò: None. F. Rocchio: None. D. Corradi: None. F. Folli: None. G. Zuccotti: None. I. Cetin: None. P. Fiorina: None.