Background The development of polycystic ovary syndrome (PCOS) is closely correlated with apoptosis and oxidative stress in ovarian granulosa cells. Kisspeptin plays an important role in reproductive organ function. This study aimed to explore the role of kisspeptin in PCOS and oxidative stress-triggered apoptosis of ovarian granular cells. Methods A PCOS rat model was established by injecting dehydroepiandrosterone (DHEA) and feeding the rats a high-fat diet. The RNA and protein levels of kisspeptin were analysed by quantitative PCR, western blotting, and histological staining. Tissue damage was evaluated using haematoxylin and eosin (H&E) staining. The viability and proliferation of human granulosa cell KGN were measured using the cell counting kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays. Cell cycle and apoptosis were analysed by flow cytometry. Oxidative stress was analysed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels. Results Kisspeptin was downregulated in the ovarian granulosa cells of PCOS rats compared to those of control rats. Kisspeptin overexpression enhanced KGN cell proliferation and inhibited apoptosis. ROS generation was suppressed by kisspeptin, along with decreased levels of MDA and increased levels of the antioxidants GSH, SOD, and CAT. Kisspeptin activates PI3K/AKT and ERK signalling, and inactivation of ERK1/2 suppresses the protective role of kisspeptin in ovarian granulosa cells. Conclusion Kisspeptin improves proliferation and alleviates apoptosis and oxidative stress in ovarian granulosa cells by activating PI3K/AKT and ERK signalling.
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It has been reported that 10 to 15% of young normogonadotrophic women show suboptimal response to standard long protocols. Letrozole (LE), an aromatase inhibitor, was shown to improve ovarian sensitivity to follicle stimulating hormone (FSH) and follicular response to gonadotrophin treatment in poor ovarian response patients. We reasoned that it might be possible to utilize LE in young normogonadotrophic patients with unexpected hypo-response in standard gonadotropin-releasing hormone agonist long protocol. A total of 652 patients defined as normogonadotrophic patients with unexpected hypo-response were divided into 2 groups, the +LE group and the +Gn group. +LE group: A fixed daily dose of 2.5 mg of LE was added on day 8 of stimulation. +Gn group: A fixed daily dose of 75 U of human menopausal gonadotrophin was added on day 8 of stimulation. The primary outcome measures were the number of oocytes obtained, fertilization rate, days of stimulation, and total FSH dosage. The secondary outcome measures were the implantation rate and ongoing pregnancy rate. There were no significant differences in the clinical and hormonal characteristics between the 2 groups. A shorter duration of stimulation and a lower dosage of recombinant FSH consumption on the day of human chorionic gonadotropin administration were all observed in the +LE group. Patients who received LE therapy showed a higher number of oocytes obtained and significantly higher fertilization rates. The implantation rate and ongoing pregnancy rate were comparable in both groups. LE significantly improves the number of oocytes obtained in patients with suboptimal response to standard gonadotropin-releasing hormone agonist long protocol.
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