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&#x2009;days; estrous cyclicity, fasting glucose, and glycated hemoglobin were monitored. After modeling, the animals underwent 28&#x2009;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 ovarianmRNA. Ovarian PPARG, P-AKT, GLUT4, INSR and IRS-1 proteins were quantified. RESULTS: Compared with the model control group, BSHT lowered serum testosterone, elevated E&#x2082; 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&#x2009;&#xb1;&#x2009;SD: 5.13&#x2009;&#xb1;&#x2009;0.27 vs 17.91&#x2009;&#xb1;&#x2009;1.19;&#x2009;<&#x2009;0.001) and up-regulated bothmRNA (0.38&#x2009;&#xb1;&#x2009;0.03 vs 0.08&#x2009;&#xb1;&#x2009;0.002;&#x2009;<&#x2009;0.001) and protein (0.37&#x2009;&#xb1;&#x2009;0.10 vs 0.12&#x2009;&#xb1;&#x2009;0.02;&#x2009;=&#x2009;0.001), while markedly increasing INSR protein abundance (1.50&#x2009;&#xb1;&#x2009;0.11 vs 0.37&#x2009;&#xb1;&#x2009;0.04;&#x2009;<&#x2009;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.