Abstract
Background
Premature ovarian insufficiency (POI) is a reproductive disorder characterized by the cessation of ovarian function before the age of 40. While mitochondrial dysfunction and immune disorders are believed to contribute to ovarian damage in POI, the interplay between these factors remains understudied in patients with this condition.
Methods
In this research, transcriptomic data related to POI were obtained from the NCBI GEO database. Hub biomarkers were identified through the construction of a protein‒protein interaction (PPI) network and further validated using RT‒qPCR. Moreover, their expression across various cell types was elucidated via single-cell RNA sequencing analysis. Comprehensive investigation into the mitochondrial and immune profiles of POI patients was carried out through correlation analysis. Furthermore, potential therapeutic agents were predicted utilizing the cMap database.
Results
A total of 119 mitochondria-related differentially expressed genes (MitoDEGs) were pinpointed, showing significant enrichment in metabolic pathways. Among these genes, Hadhb, Cpt1a, Mrpl12, and Mrps7 were confirmed both in a POI model and in human granulosa cells (GCs), where they were found to accumulate in GCs and theca cells. Immune analysis revealed variations in macrophages, monocytes, and 15 other immune cell types between the POI and control groups. Notably, strong correlations were observed between seven hub-MitoDEGs (Hadhb, Cpt1a, Cpt2, Mrpl12, Mrps7, Mrps51, and Eci1) and various aspects such as mitochondrial respiratory complexes, dynamics, mitophagy, mitochondrial metabolism, immune-related genes, and immunocytes. Additionally, nine potential drugs (calyculin, amodiaquine, eudesmic acid, cefotaxime, BX-912, prostratin, SCH-79797, HU-211, and pizotifen) targeting key genes were identified.
Conclusions
Our results highlight the crosstalk between mitochondrial function and the immune response in the development of POI. The identification of MitoDEGs could lead to reliable biomarkers for the early diagnosis, monitoring and personalized treatment of POI patients.