Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia

Abstract

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are associated with maternal and infant health. Although the pathogenesis of PE and GDM remains controversial, oxidative stress is involved in the underlying pathology of GDM and PE. Protein lysine acetylation (Kac) plays an important regulatory role in biological processes. There is little data regarding the association of the maternal acetylome with GDM and PE. This study aimed to assess the potential value of the proteome and acetylome for GDM and PE. In our study, we included placental tissues from healthy individuals (n = 6), GDM patients (n = 6), and PE patients (n = 6) to perform 4D-label free quantification proteomics analysis and PRM analysis. We identified 22 significantly regulated proteins and 192 significantly regulated acetylated proteins between the GDM and PE groups. Furthermore, 192 significantly regulated acetylated proteins were mainly enriched in endoplasmic reticulum stress (ERS) and ferroptosis pathways. Seventeen acetylated sites in these two pathways were verified by PRM analysis. Our comprehensive analysis revealed key features of GDM/PE-significantly regulated acetylated proteins in the placentas from GDM and PE. The results of signaling pathway analysis focused on ERS and ferroptosis. These findings may help

Sex-Specific Alterations in Placental Proteomics Induced by Intrauterine Hyperglycemia

“…This dissimilarity may be due to variations among the individual samples and differences between the human and murine specimens. In a similar vein, Hu et al 21 also reported an upregulation of cell oxidant detoxification mechanisms in GDM placentas, which aligns with our findings. Additionally, Assi's research 22 indicated alterations in the enrichment of pathways related to oxidative stress, metabolic processes, and complement and coagulation cascades, further supporting our observations.…”

Role of ferroptosis in pregnancy related diseases and its therapeutic potential

“…GDM is associated with long-lasting complications in the short and long term, such as macrosomia ( Song et al, 2022 ), dystocia ( Crowther et al, 2022 ), childhood obesity in the child ( Choi et al, 2022 ), recurrence of GDM ( Giuliani et al, 2022 ), developing type 2 diabetes ( Vounzoulaki et al, 2020 ) and cardiovascular disease in the mother ( Christensen et al, 2022 ). Emerging evidence suggests ferroptosis contributes to the pathogenesis of GDM ( Han et al, 2020 ; Gautam et al, 2021 ; Zhang et al, 2022c ; Hu et al, 2022 ; Zaugg et al, 2022 ). The insulin sensitivity shifts depending on the requirements of pregnancy, which is an important metabolic adaptation during healthy pregnancy ( Di Cianni et al, 2003 ).…”