Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study.

BACKGROUND: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. OBJECTIVE: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. METHODS: We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. RESULTS: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. CONCLUSION: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.

Enantioselective [4 + 1]-Annulation of α,ß-Unsaturated Imines with Allylic Carbonates Catalyzed by a Hybrid P-Chiral Phosphine Oxide-Phosphine.

A highly enantio- and diastereoselective [4 + 1]-annulation reaction between α,ß-unsaturated imines and allylic carbonates has been realized under the catalysis of a novel hybrid P-chiral phosphine oxide-phosphine, providing enantioenriched polysubstituted 2-pyrrolines in good to excellent yields and up to 99% ee. Based on Han's methods, the catalyst featuring a sole P(O)-chirality in the molecule is readily accessible and represents a class of new chiral phosphine organocatalysts. In the plausible catalytic mechanism, an intramolecular Coulombic interaction between the in situ generated phosphonium cation and polar chiral P═O moiety may play a positive role.