Scope: Insulin resistance (IR) has a close relationship with the main clinical manifestations of patients with PCOS; hence, the research and development of new drugs to treat PCOS by improving IR is a desiderate task at present. Resveratrol (RES) possesses a variety of beneficial pharmacological functions, such as antioxidation, anti-inflammatory, regulating glucose, and lipid metabolism. However, whether RES could improve IR and the underlying mechanisms remained unclear in PCOS.Methods and results: SD rats received a high-fat diet and letrozole for 30 days to establish the PCOS model and then intervened with RES for 30 days. The results demonstrated that RES played a protective role on the IR in PCOS rats, which significantly decreased the levels of blood glucose and serum insulin, up regulated the expression of IGF1R, and down regulated the expression of IGF1. In vitro, KGN cells were treated with insulin, RES, and AGK2, respectively. We found that a high dose of insulin (4μg/mL) significantly inhibited KGN cell viability, decreased the level of lactic acid, and increased the level of pyruvate, while RES (25μM) attenuated the growth-inhibitory effect, as well as increased the level of lactic acid and decreased the level of pyruvate after high levels of insulin treatment. Simultaneously, RES up regulated the expression level of the crucial rate-limiting enzymes relating to glycolytic pathways, such as LDHA, HK2, and PKM2. Furthermore, AGK2 remarkably inhibited the expression level of SIRT2, which was similar to the same negative effects processed by insulin. Meanwhile, RES overtly repaired the glycolysis process by reversing the levels of lactic acid and pyruvate, together with up regulating the expression level of LDHA, HK2, and PKM2, after AGK2 treatment.Conclusion: RES could effectively improve insulin resistance and restore the glycolysis pathway by regulating SIRT2, which may contribute to attenuating the ovarian damage of PCOS rats and provide a potential treatment for patients with PCOS.

Background: The present study performed two distinct meta-analyses with common outcomes (sperm parameters); one was performed in obese individuals (and non-obese controls) and the other in diabetic individuals (and non-diabetic controls). Methods: PubMed, Embase, The Cochrane library, Web of Science, Scopus databases were searched to collect clinical studies related to the effects of obesity and diabetes on male sperm from inception to on 1st February 2021. Statistical meta-analyses were performed using the RevMan 5.4 software. Stata16 software was used to detect publication bias. The methodological quality of the included studies was assessed with the Ottawa–Newcastle scale using a star-based system. Results: A total of 44 studies were finally included in the present study, which enrolled 20,367 obese patients and 1386 patients with diabetes. The meta-analysis results showed that both obesity and diabetes were associated with reduced semen volume (obese versus non-obese controls: mean difference (MD) = − 0.25, 95% CI = (− 0.33, − 0.16), p < 0.001; diabetes versus non-diabetic controls: MD = − 0.45, 95% CI = (− 0.63, − 0.27), p < 0.001), reduced sperm count (obese versus non-obese controls: MD = − 23.84, 95% CI = (− 30.36, − 17.33), p < 0.001; diabetes versus non-diabetic controls: MD = − 13.12, 95% CI = (− 18.43, − 7.82), p < 0.001), reduced sperm concentration (obese versus non-obese controls: MD = − 7.26, 95% CI = (− 10.07, − 4.46), p < 0.001; diabetes versus non-diabetic controls: MD = − 11.73, 95% CI = (− 21.44, − 2.01), p = 0.02), reduced progressive motility (obese versus non-obese controls: MD = − 5.68, 95% CI = (− 8.79, − 2.56), p < 0.001; diabetes versus non-diabetic controls: MD = − 14.37, 95% CI = (− 21.79, − 6.96), p = 0.001), and decreased testosterone levels (obese versus non-obese controls: MD = − 1.11, 95% CI = (− 1.92, − 0.30), p = 0.007; diabetes versus non-diabetic controls: MD = − 0.37, 95% CI = (− 0.63, − 0.12), p = 0.004). Conclusions: Current evidence suggests that obesity and diabetes negatively affect sperm parameters in men and are associated with low testosterone levels. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Patients with Polycystic ovary syndrome (PCOS) have chronic low-grade ovarian inflammation. Inflammation can cause telomere dysfunction, and telomere and telomerase complex are also involved in regulating inflammation. However, the specific mechanisms of inflammatory signaling feedback and telomere-telomerase mutual regulation remain to be discovered. This study elucidates the role of Nuclear factor kappa-B (NF-κB)-Telomerase reverse transcriptase (TERT) feedback in PCOS granulosa cell apoptosis. Using letrozole and a high-fat diet, a PCOS rat model was established, along with a Lipopolysaccharide (LPS) -treated KGN cell inflammation model was established. NF-κB and TERT inhibitors (BAY 11–7082 and BIBR1532) were then administered to LPS-induced KGN cells. PCOS rats displayed disrupted estrous cycles, increased weight, elevated serum testosterone, cystic follicles, granulosa cell layer thinning, and reduced corpora lutea count (P are all less than 0.05). In PCOS rat ovaries, NF-κB, Interleukin-6 (IL-6), Tumor Necrosis Factor α (TNF-α), TERT, Bax, and Caspase-3 exhibited notable upregulation, while Bcl-2 decreased, with telomere elongation (P are all less than 0.05). There were significant correlations among NF-κB-related inflammatory factors, TERT and apoptotic factors, and they were positively correlated with Bax and Caspase-3, and negatively correlated with Bcl-2 (P are all less than 0.05). LPS-treated KGN cells demonstrated increased expression of inflammatory and pro-apoptotic factors, later restored post-treatment with NF-κB and TERT inhibitors (P are all less than 0.05). In conclusion, TERT may induce granulosa cell apoptosis by participating in the regulation of the NF-κB signaling pathway, thereby mediating the chronic inflammatory response of PCOS through downstream inflammatory factors IL-6 and TNF-α.

This study aimed to determine the correlation between amino acid profiling of a 3-day-old embryo culture medium and embryo implantation potential in women undergoing in vitro fertilization (IVF). The data of 98 patients who received IVF treatment in our hospital from December 2015 to February 2017 were retrospectively analyzed. The 98 patients were grouped into a pregnant group (gemellary pregnancy), a non-pregnant group (non-pregnancy), and a blank control group. The amino acids from a 3-day-old embryo culture medium and blank control medium were collected and were analyzed using high performance liquid chromatography (HPLC). The HPLC results showed that amino acids including aspartate (ASP), serine (SER), glycine (GLY), histidine (HIS), taurine (TAU), arginine (ARG), threonine (THR), alanine (ALA), and proline (PRO) were detected in the 3-day-old embryo culture medium and blank control medium. There are significant differences between the pregnant group and non-pregnant group in peak height (H)-SER, surface area (S)-ASP, S-SER, S-HIS, and S-ALA. The discrimination analysis according to the peak height and peak area of amino acids revealed that the prediction rate of the pregnant group, non-pregnant group, and blank control group were 82.7, 95.7, and 100%. Further, by using the principal component analysis, we found that the prediction rate in these three groups were 90.4, 91.3, and 100%. Our data may suggest that using amino acid concentrations for principal component analysis and discriminant analysis has high accuracy in predicting the relationship between amino acid fingerprint and embryo implantation potential.

Aim: This study systematically evaluated the potential efficacy of serum matrix metalloproteinase-9 (MMP-9) concentration as a diagnostic marker for endometriosis through meta-analysis. Early and accurate diagnosis of endometriosis, a common gynecological disease, is crucial for improving patient prognosis. Hence, this study aimed to comprehensively analyze the data from multiple studies to assess the diagnostic value of serum MMP-9 concentration for endometriosis.Methods: Articles investigating the association between MMP-9 and endometriosis, published from the inception of the databases until February 2024, were systematically retrieved from multiple databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and CNKI. Download and analyze the GSE7305, GSE23339, and GSE51981 datasets. Statistical analyses of all eligible studies were conducted using RevMan 5.4, Stata 11.0, and R software version 4.3.3.Results: Fifteen studies fully met the inclusion criteria for the meta-analysis. The concentration of MMP-9 in the blood of patients with endometriosis was significantly higher compared to that of the control group (p < 0.0001). Subgroup analysis based on different stages of endometriosis revealed a trend towards significantly higher serum MMP-9 concentrations in patients, whether in stages I-II or III-IV. Bioinformatics analysis revealed differences in the expression of MMP-9 in endometrial tissue between EMT patients and healthy controls in the GSE7305 and GSE23339 datasets. Additionally, in the GSE51981 dataset, we found significant differences between the normal group and both mild and severe cases of endometriosis.Conclusion: Both the current meta-analysis and bioinformatics analysis indicate differences in MMP-9 concentration levels between endometriosis patients and healthy individuals, with potentially elevated MMP-9 concentrations in serum samples from patients with endometriosis.Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024525864.