Perinatal changes in plasma of type 2 diabetes mellitus pregnancies who delivered newborns with cardiomyopathy, depression of the central nervous system, or hepatomegaly

Abstract

Background Maternal diabetes either pregestational or gestational is the main risk factor contributing in development of diabetic fetopathy (DF) in newborns. There are no generalized signs of DF up to late gestational age due to insufficient sensitivity of the currently employed instrumental methods for diagnosis. Methods This is a cross-sectional prospective controlled study. Here, we reported proteomic investigation for several cases of severe types of diabetic fetopathy (cardiomyopathy (CRDM, n = 37), central nervous system depression (CNSD, n = 35) and hepatomegaly (HPMG, n = 35)) diagnosed during 30–35 gestational weeks and confirmed upon delivery by from patients with type 2 diabetes mellitus (T2DM). Control groups were comprised from women in whom T2DM had been ruled out (n = 40) and group of pregnancies with T2DM who delivered healthy newborns (n = 40). Results We found a composition of serum-based non-trivial markers capable that are strongly associated with the certain type of fetopathy or anatomical malfunctions in the affected newborns. Significant impact on mRNA splicing and DNA reparation has been determined by emerging alterations in CDCL5. Patients of CNSD groups were characterized by utmost depletion (ca. 7% of baseline) of DFP3 neurotrophic factor needed for the proper specialization of cardiomyocytes and oligodendrocytes. Corrupted regulation of non-canonical Wnt-signaling guided by PEDF (in CNSD and HPMG groups) and DAAM2 (in CRDM and HPMG groups) was also proposed. In addition, deficiency in retinoic acid and thyroxine transport was revealed by dramatic increase of TTHY in CNDS group. Conclusions We examined peripheral blood plasma and determined a small proportion of proteins indicating the pre-existing signs of DF. Most of the examined markers are participants of critical processes at different stages of embryogenesis and regulate various phases of morphogenesis. There are proteins regulating splicing and DNA repair, differentiation of neurons and their switching to the post-mitotic state. Therefore, reconstruction of the molecular interplay between the defined in proteins is decisive to appreciate cryptic violations in fetal development on the background of diabetic conditions