Liang Zilong, Hu Conglei, Pang Haofeng, Sha Yi, Lv Jizong, Wu Guanyu, Du Haiyang, Hao Liangliang, Yao Liping, Liu Fei
Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China.
Department of Urology, Air Force Medical Center of PLA, Air Force Medical University, Beijing, China.
Transl Androl Urol. 2025 Apr 30;14(4):964-973. doi: 10.21037/tau-2024-657. Epub 2025 Apr 27.
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.
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.
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.
These results suggest that there is a potential causal relationship between some immune cell subtypes and male infertility at the genetic level.
流行病学研究表明，早期免疫炎症反应与男性不育症相关，细菌和病毒通过其独特结构与宿主的免疫和炎症系统相互作用。本研究旨在利用孟德尔随机化（MR）来探究不同免疫细胞类型与男性不育风险之间的因果关系。
男性不育数据来自芬兰基因数据库，免疫细胞亚型数据则从全基因组关联研究（GWAS）目录中收集。进行了MR分析以研究免疫细胞与男性不育之间的因果关系。采用了几种MR方法，包括逆方差加权（IVW）、加权中位数、加权模式、MR-Egger和简单模式。还进行了反向MR分析以探索反向因果关系。进行了敏感性分析，包括用于异质性的Cochran Q检验、用于多效性的MR-Egger回归以及用于排除多效性异常值的MR-PRESSO，以评估研究结果的稳健性。
该研究确定了23种与男性不育有因果关系的免疫表型，其中六种免疫表型具有保护作用，17种为风险因素。在反向MR分析中未发现男性不育与免疫表型之间存在反向因果关系。
这些结果表明，在基因水平上，某些免疫细胞亚型与男性不育之间存在潜在的因果关系。
