Molecular stratification of ovarian insufficiency via novel MicroRNA signatures and target gene suppression

Diminished ovarian reserve (DOR) and premature ovarian failure (POF) are ovarian dysfunctions before age 40, with miRNAs implicated in their pathophysiology. This study evaluated IGF1R, POU2F, and potential regulators miR-507, miR-761, and miR-4770 across healthy, DOR, and POF groups.

Follicular fluid (FF), granulosa cells (GCs), and blood serum (BS) were obtained from 25 healthy controls undergoing ART for male-factor infertility, 25 DOR, and 15 POF patients. IGF1R/POU2F expression in GCs and miRNA levels in all samples were assessed by qRT-PCR.

All miRs were significantly downregulated in FF of DOR patients. On the other hand, miR-507 was significantly reduced in GCs. miR-761 was also reduced in GCs but not significant, while miR-4770 remained unchanged (P ≥ 0.05). In serum, both miR-507 and miR-761 were decreased in DOR and POF patients vs. controls, whereas miR-4770 yielded inconsistent results. ROC analysis confirmed that miR-507 as a strong serum marker, can distinguish DOR and POF patients from Normal individuals in all types of samples. Moreover, miR-761 can distinct patient from healthy cases. In addition, miR-4770 in FF can differentiate DOR and POF from normal controls. Also, IGF1R and POU2F were downregulated in GCs of DOR patients.

Our results reveal that miR-507, miR-761and selected genes were differentially expressed between healthy controls and DOR/POF patients and were associated with the progression of POF, suggesting that these miRNAs reflect the presence of ovarian dysfunction rather than its specific severity or stage. These data suggest their potential as predictive biomarkers for molecular detection of POF.