Interplay between miR-21 and mTOR signaling in an experimental mouse model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), one of the leading causes of anovulatory infertility, is a complex endocrinopathy influenced by environmental factors. Evidence suggests a connection between PCOS and mammalian target of rapamycin (mTOR), a serine/threonine kinase involved in cellular growth, proliferation, and metabolism. MicroRNA-21(miR-21), a key post-transcriptional regulator of ovarian function, is also implicated in follicular development, atresia, and steroidogenesis. This study aimed to investigate the relationship between miR-21 and mTOR in an experimental PCOS mouse model.Forty-two Balb/c female mice (25-day-old) were divided into six groups: Control, SO (PCOS vehicle-control), PCOS, Inhibition, PCOS+Inhibition, and DMSO (mTOR inhibition-vehicle-control. PCOS was induced via subcutaneous injection of dehydroepiandrosterone (6 mg/100 g), and mTOR inhibition was achieved with KU-0063794 (1 mg/100 g). Serum estrogen (E2) and progesterone (P4) levels were measured by ELISA. Ovarian tissues were evaluated histomorphologically and immunohistochemically.Compared with controls, PCOS mice exhibited increased body weight (p < 0.05), elevated serum E2 (p < 0.001), P4 (p < 0.01) and cystic follicles, reduced corpora lutea (p < 0.001), and enhanced mTOR/p-mTOR and PCNA immunoreactivity (p < 0.001). In the PCOS + INH group, mTOR and p-mTOR immunoreactivity were significantly reduced compared with PCOS (p < 0.001), and DHEA-induced weight gain was attenuated; however, E2 remained elevated (p < 0.001) and corpora lutea were not restored (p < 0.001). miR-21 expression was significantly upregulated in both PCOS (p < 0.05)-PCOS + INH (p < 0.001) groups, indicating persistent miR-21 activation despite mTOR inhibition.These findings demonstrate that while mTOR signaling is activated in PCOS and may be pharmacologically suppressed, mTOR inhibition alone is insufficient to normalize steroidogenesis, ovulation, or miR-21 expression, suggesting mTOR-independent regulation of miR-21 in this model.