Immune-molecular nexus in reproductive disorders: mechanisms linking POI and RSA

Area of Science:

• Genomics and Bioinformatics
• Reproductive Medicine
• Immunology

Background:

• Female infertility, including Premature Ovarian Insufficiency (POI) and Recurrent Spontaneous Abortion (RSA), is a significant global health issue.
• Identifying novel molecular targets is crucial for developing effective treatments for these conditions.

Purpose of the Study:

• To identify central genes and potential therapeutic drugs for RSA and POI using integrated multi-transcriptome data and machine learning.
• To elucidate the molecular mechanisms underlying POI and RSA and uncover potential therapeutic interventions.

Main Methods:

• RNA sequencing data from POI and RSA patients were analyzed using machine learning algorithms (mCODE, Cytoscape).
• Comprehensive evaluations included functional annotation, protein-protein interaction (PPI) networks, gene regulatory networks (TF-miRNA), GSEA, and immune infiltration analysis.
• Drug target enrichment analysis and qRT-PCR validation were performed on granulosa cells and endometrial tissues.

Main Results:

• Six hub genes (CENPW, ENTPD3, FOXM1, GNAQ, LYPLA1, PLA2G4A) were identified as key players in POI and RSA.
• Immune cell analysis revealed increased activated NK cells and altered proportions of other immune cells.
• These genes are involved in oxidative phosphorylation, ribosome biogenesis, and steroid biosynthesis, with ten potential drugs identified for targeted therapy.

Conclusions:

• The identified hub genes and targeted drugs show promise for preventing and treating POI and RSA.
• This research provides critical molecular insights for addressing complex female infertility conditions.