Bushen Huatan formula improves reproductive and endocrine metabolic disorders in non-obese polycystic ovary syndrome rats via adipose tissue-derived exosomal miR-27a-3p/PPARG signaling pathway.

Abstract

Objectives: This study aims to investigate the therapeutic effects of the Bushen Huatan (BSHT) Formula on non-obese polycystic ovary syndrome (PCOS) rats, and to explore its potential mechanisms of action.

Methods: A PCOS model was induced in rats via letrozole, a high-fat/high-sucrose diet, and a PEPD inhibitor for 35 days; estrous cyclicity, fasting glucose, and glycated hemoglobin were monitored. After modeling, the animals underwent 28 days of assigned treatment, followed by an oral glucose tolerance test (OGTT) and assays for sex steroids and lipids. Ovarian and hepatic histology and hepatic steatosis were evaluated. Adipose-derived exosomes were characterized for size, concentration, and surface markers (TSG101, HSP70, CD63). Detect the expression levels of adipose tissue-derived exosomal microRNA-27a-3p (AT-EXO-miR-27a-3p) and ovarian Pparg mRNA. Ovarian PPARG, P-AKT, GLUT4, INSR and IRS-1 proteins were quantified.

Results: Compared with the model control group, BSHT lowered serum testosterone, elevated E₂ and FSH, ameliorated glucose intolerance, and improved lipid profiles by decreasing TC and TG and increasing HDL-C. Polycystic ovarian morphology and hepatic lipid accumulation were also attenuated. BSHT down-regulated AT-EXO-miR-27a-3p expression (mean ± SD: 5.13 ± 0.27 vs 17.91 ± 1.19; p < 0.001) and up-regulated both Pparg mRNA (0.38 ± 0.03 vs 0.08 ± 0.002; p < 0.001) and protein (0.37 ± 0.10 vs 0.12 ± 0.02; p = 0.001), while markedly increasing INSR protein abundance (1.50 ± 0.11 vs 0.37 ± 0.04; p < 0.001).

Conclusions: This study demonstrates that the BSHT prescription may alleviate reproductive endocrine disorders in PCOS rats by mitigating the inhibitory effects of fat-derived exosomal miR-27a-3p on PPARG.