Context Advanced maternal age (especially over 40 years) shows markedly declined fertility, although the exact mechanisms remain unclear. Exosomal microRNAs (miRNAs) within follicular fluid (FF) regulate granulosa cell (GC) functions, thereby inducing alterations in the metabolic features of the FF. However, the specific dysregulation and functional impact of this exosomal miRNA–GC axis in the context of ovarian aging require further elucidation. Aims To delineate the distinct expression profiles of FF exosomal miRNAs and GC mRNAs, coupled with FF metabolic features, in women of advanced maternal age, and to explore the integrated regulatory networks linking these components. Methods FF samples were collected from the aged group (≥40 years, n = 19) and young group (≤30 years, n = 19). Centrifugation separated it into GCs, exosomes, and the remaining FF containing metabolites. Each fraction was analyzed for differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differential metabolites (DMs). Key results Analysis identified 373 DEmRNAs, 50 exosomal DEmiRNAs (targeting 2633 genes), and 97 DMs. Integrated correlation analysis pinpointed a core regulatory axis, hsa-miR-132-3pCHAC1, which was strongly associated with four key metabolites (7-HOCA, Lysopc (18: 1), 9 (S) -Hpode, Androsterone Sulfate). This axis potentially disrupts cellular redox homeostasis. Conclusions Multiomics analysis uncovered a dysregulated FF exosomal miRNAGC mRNAₘetabolite network in women of advanced maternal age compared with the young group, with the hsa-miR-132-3pCHAC1 axis potentially mediating age-related ovarian dysfunction via perturbed cellular redox homeostasis. Implications This study offers insights into the mechanisms underlying the age-related decline in female fertility.
Li et al. (Mon,) studied this question.