Genetic predisposition to female infertility in relation to epithelial ovarian and endometrial cancers.

BACKGROUND: The associations between female infertility and epithelial ovarian cancer (EOC) or endometrial cancer (EC) have been reported in observational studies, but its causal relationship remains unknown. We intended to assess the causal effect of female infertility on EOCs and ECs using a two-sample Mendelian Randomization (MR) approach. METHODS: Large pooled genome-wide association study (GWAS) datasets for female infertility (6481 cases and 68 969 controls), EOC (25 509 cases and 40 941 controls), and EC (12 906 cases and 108 979 controls) were derived from public GWAS databases and published studies. The Inverse Variance Weighted method, Weighted Median method, MR-Egger regression, and MR-Pleiotropy Residual Sum and Outlier test were adopted for MR analyses. RESULTS: Our results suggested that genetically predicted infertility was positively associated with the risk of EOC (OR = 1.117, 95% CI = 1.003-1.245, P = .045), but did not find a causal relationship between infertility and EC (OR = 1.081, 95% CI = 0.954-1.224, P = .223). As to the reverse direction, our study did not obtain evidence from genetics that EOCs (OR = 0.974, 95% CI = 0.825-1.150, P = .755) and ECs (OR = 1.039, 95% CI = 0.917-1.177, P = .548) were associated with an increased risk of infertility. CONCLUSIONS: This large MR analysis supported a causal association between female infertility and increased risk of EOCs, but did not find a causal relationship between infertility and ECs.

Activation of the hippocampal AC-cAMP-PKA-CREB-BDNF signaling pathway using WTKYR in depression model rats.

Depression, also called "depression disorder," is characterized by a significant and persistent low mood. It has become a major refractory disease in the 21st century. In recent years, Chinese medicine has shown some important clinical value in the treatment of depression. Among them, the Warming and "Tonifying" Kidney-Yang Recipe (WTKYR) has been demonstrated to have obvious effects in the clinical treatments of depression; however, the mechanism remains unclear. This study is based on the adenylyl cyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway, aiming to investigate the mechanism of WTKYR. The results showed that WTKYR can upregulate AC-cAMP-PKA-CREB-BDNF in the hippocampus of depression model rats and alleviate its depressive symptoms, which may be the mechanism of WTKYR.