Disruption of Mitophagy-Related Gene Expression in Gestational Diabetes Mellitus: A Transcriptomic and Machine...

Area of Science:

• Mitochondrial biology
• Genetics
• Reproductive medicine

Background:

• Gestational diabetes mellitus (GDM) is a pregnancy complication associated with adverse outcomes.
• Mitochondrial dysfunction is implicated in GDM pathogenesis.
• The role of mitophagy in GDM is not well understood.

Purpose of the Study:

• To investigate the expression and regulation of mitophagy-related genes (MRGs) in GDM.
• To identify potential biomarkers for GDM using transcriptomic data.

Main Methods:

• Analysis of publicly available RNA-seq datasets (GSE203346, GSE154414, GSE154377).
• Differential expression analysis of 65 MRGs using edgeR and DESeq2.
• Machine learning for temporal expression modeling and classification.

Main Results:

• Four key MRGs (MUL1, PINK1, TOMM7, ATF4) were consistently downregulated in GDM placental tissue and cord blood.
• Temporal regulation patterns of these MRGs were disrupted in GDM pregnancies.
• Functional enrichment revealed impaired mitochondrial import, autophagy, and oxidative stress responses in GDM.

Conclusions:

• Mitophagy dysregulation is an early and persistent feature of GDM.
• MUL1, PINK1, TOMM7, and ATF4 are potential biomarkers and therapeutic targets for GDM.
• Tissue-specific analysis is crucial, as MRG alterations were not observed in maternal plasma.