Epigenetic dysregulation of steroidogenesis and neuroactive steroid deficiency in premature ovarian insufficiency: implications for neurodegenerative risk.

ABSTRACT: Premature ovarian insufficiency (POI) is associated with an increased risk of neurodegenerative diseases, but the underlying mechanisms remain unclear. Here, we integrated DNA methylome profiling of peripheral blood leukocytes and circulating steroid hormone analysis to identify potential mechanism linking POI to neurogenerative risk. Methylome analysis revealed distinct epigenetic signatures in POI patients, including hypomethylation at the SOAT1 promoter, a gene critical for cholesterol homeostasis. Gene set enrichment analysis (GSEA) implicated suppressed steroid biosynthesis, supported by significantly reduced circulating levels of steroids, including androstenedione, dehydroepiandrosterone (DHEA), aldosterone, cortisol, and cortisone in POI patients. Notably, neuroprotective steroids

SUBMITTER: Wang Q 

PROVIDER: S-EPMC12613854 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature