Mogroside V Improves Follicular Development and Ovulation in Young-Adult PCOS Rats Induced by Letrozole and High-Fat Diet Through Promoting Glycolysis.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. In this study, we induced a young-adult PCOS rat model by oral administration of letrozole combined with a high-fat diet and then treated with mogroside V (MV) to evaluate the protective effects of MV on endocrine and follicle development in young-adult PCOS rats. MV (600 mg/kg/day) administration not only significantly reduced the body weight and ovary weight, but also attenuated the disrupted estrous cycle and decreased the level of testosterone. MV restored the follicular development, especially by increasing the number of corpus luteum and the thickness of the granular layer in young-adult POCS rats. Moreover, metabolomics showed that MV markedly increased the levels of D-Glucose 6-phosphate, lactate and GTP, while decreased the level of pyruvate. Bioinformatic analysis revealed that MV recovered multiple metabolism-related processes including gluconeogenesis, glycolysis and glucose metabolic process. Further real-time quantitative PCR analysis showed that MV upregulated the expression of lactate dehydrogenase A (Ldha), hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2). Western blotting and immunohistochemistry analysis showed that MV restored the expression of lactate dehydrogenase A (Ldha), hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2). Collectively, these findings indicated that MV could effectively improve the ovarian microenvironment by upregulating the expression of LDHA, HK2 and PKM2 in granulosa cells and enhancing lactate and energy production, which may contribute to follicle development and ovulation of young-adult PCOS rats.

Resveratrol Improves Follicular Development of PCOS Rats by Regulating the Glycolytic Pathway.

SCOPE: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility; however, the underlying mechanisms remain ill-defined, and there are no available drugs or strategies for the treatment of PCOS. This study examined the therapeutic effect of resveratrol in a rat model of PCOS. METHODS AND RESULTS: PCOS is induced in rats by administration of letrozole and a high fat diet to determine whether resveratrol has a protective effect. Oral administration of resveratrol significantly decreased body weight, as well as the serum levels of testosterone and follicle stimulating hormone. Resveratrol improved the estrous cycle by restoring the thickness and number of granular cells. Resveratrol increased the levels of lactate and ATP, decreased pyruvate levels, and restored the glycolytic process, upregulating LDHA, HK2, and PKM2. Resveratrol also upregulated SIRT2, thereby modulating the expression of rate-limiting enzymes of glycolysis. CONCLUSION: Resveratrol suppressed damage to the ovaries in PCOS rats by restoring glycolytic activity, providing potential targets for the treatment of PCOS.

Dendrobium nobile Lindl. polysaccharides improve follicular development in PCOS rats.

Polycystic ovary syndrome (PCOS) is the most typical and common metabolic abnormalities in women of reproductive age. This study examined the protective effects of Dendrobium nobile Lindl. polysaccharides (DNLP) on ovarian follicular development in letrozole-induced PCOS rats and explored the underlying molecular mechanisms. The PCOS rats showed the increased body weight, serum testosterone and luteinizing hormone levels and insulin resistance. DNLP treatment reduced the body weight, serum testosterone level and insulin resistance, but failed to affect luteinizing hormone level in the PCOS rats. DNLP treatment recovered disrupted estrous cycle in the PCOS rats. DNLP treatment decreased antral follicles and increased the thickness of the granular cell layer. DNLP treatment increased the PCNA mRNA and protein expression levels in the PCOS ovarian tissues, and inhibited cell apoptosis in the PCOS ovarian tissues via regulating apoptosis-related proteins including Bax, Bcl-2 and caspase-3. In summary, this study demonstrated the protective effects of DNLP on the ovaries in the letrozole-induced PCOS rat model. DNLP exerted its protective effects via improving follicular development and inhibiting apoptosis of ovarian granular cells in PCOS rats. This study will provide experimental basis for the future clinical application of DNLP in the treatment of PCOS.