Background
Evidence from observational studies has suggested a link between cigarette smoking and the risk of polycystic ovary syndrome (PCOS). However, it remains uncertain whether the observed relationship is causal or due to biases inherent in observational studies. Therefore, we adopted two-sample Mendelian randomization (MR) design to assess the potential causal association between smoking and the risk of PCOS.
Methods
Summary level data of PCOS was obtained from a genome-wide association study (GWAS) meta-analysis including 4,138 cases and 20,129 controls of European ancestry. Single-nucleotide polymorphisms (SNPs) associated with smoking initiation (n=360) were selected and used as genetic instrumental variables (IVs). MR analysis was performed using inverse-variance weighted (IVW) method, supplemented with the likelihood-based method, weighted median method, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and MR-Egger regression.
Results
Genetically predicted smoking initiation was associated with an increased risk of PCOS in the primary analysis (odds ratio (OR) =1.38, 95% confidence interval (CI) =1.12–1.69). MR-Egger regression did not detect the horizontal pleiotropy. Sensitivity analyses using alternative MR methods and restricted IVs produced similar results.
Conclusion
Our study provided evidence to support a potential causal association between smoking initiation and an increased risk of PCOS, providing a better understanding of the etiology and prevention of PCOS. Further studies are warranted to clarify the underlying biological mechanisms of smoking in the development of PCOS.
Purpose: To study the effect of metformin on polycystic ovarian syndrome (PCOS) and insulin resistance (IR) in rats, and the mechanism involved.Methods: Eighty healthy female SD rats, aged 6 weeks, were selected. Three groups of rats were used: model, metformin + PI3K inhibitor, and metformin groups, with 20/group. Testosterone, leutenizing hormone (LH), and follicle-stimulating hormone (FSH) were assayed by enzyme-linkedassay (ELISA), while HOMA-IR was calculated from fasting blood sugar (FBG); the effect of metformin on the IR of PCOS rats was determined. The expressions of PI3K and AKT in ovaries and liver of rats in each group were assayed by Western blotting.Results: Fasting blood glucose, fasting insulin, and insulin resistance index were markedly higher in model than in control rats, and also significantly higher in inhibitor-treated rats than in metformin rats (p < 0.05). Relative to control, FSH level was higher, while levels of LH, LH/FSH ratio and testosterone in the metformin group were significantly lower (p < 0.05). The expression levels of PI3K and AKT in the ovary and liver were reduced in the inhibitor group, relative to the levels in metformin-treated rats (p < 0.05).Conclusion: Metformin mitigates PCOS-linked ovarian changes and IR in rats via PI3K/AKT route. These findings may be useful in the design of new drugs.
Keywords: Metformin, Polycystic ovary syndrome, Leutenizing hormone, Insulin resistance, Fasting blood sugar, Follicle-stimulating hormone
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