Causal role of immune cells in male infertility: a Mendelian randomization study.

Background: Epidemiological studies have shown that early immune inflammatory responses are associated with male infertility, and bacteria and viruses interact with the host's immune and inflammatory systems through their unique structures. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between different immune cell types and the risk of male infertility. Methods: Male infertility data was obtained from the FinnGen database, and immune cell subtypes data were gathered from the Genome-Wide Association Studies (GWAS) catalog. An MR analysis was performed to investigate the causal relationship between immune cells and male infertility. Several MR methods, including inverse-variance weighted (IVW), weighted median, weighted mode, MR-Egger, and simple mode, were employed. Reverse MR analysis was also conducted to explore the reverse causal relationship. Sensitivity analyses, including Cochran's Q test for heterogeneity, MR-Egger regression for pleiotropy, and MR-PRESSO to exclude pleiotropic outliers, were performed to assess the robustness of the findings. Results: The study identified 23 immune phenotypes causally associated with male infertility, of which six immune phenotypes were protective, and 17 were risk factors. No reverse causal relationship was found between male infertility and immune phenotypes in the reverse MR analysis. Conclusions: These results suggest that there is a potential causal relationship between some immune cell subtypes and male infertility at the genetic level.