Wang Jinyuan, Long Haojun, Su Mingxuan, Cao Yichang, Zhou Runtang, Li Xiang, Li Jiangming, Tang Yuxia, Tang Jiayi, Wang Simin, Tang Linyue, Chen Ruxin, Deng Danqi, Tang Li
Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.
Reprod Toxicol. 2025 Jul 2;137:108984. doi: 10.1016/j.reprotox.2025.108984.
Infertility is viewed as a significant social challenge globally. Numerous observational studies have documented the link between autoimmune diseases (ADs) and female infertility, yet the underlying cause remained unclear. The primary objective of this study was to ascertain the causal connection between ADs and female infertility.
We evaluated summary statistics from genome-wide association studies (GWAS) for prevalent autoimmune diseases (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1DM), celiac disease (CeD), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis and female infertility. Initial two-sample Mendelian randomization (MR) analyses was conducted to pinpoint causal autoimmune diseases associated with female infertility in the discovery and replication analysis.
Our two-sample Mendelian randomization analysis, using data from the UK Biobank and FinnGen (or IIBDGC), provided evidence for a causal association between genetically predicted rheumatoid arthritis (RA), type 1 diabetes (T1DM), celiac disease (CeD), and ulcerative colitis (UC) and an increased risk of female infertility. These associations were observed across different sub-phenotypes of infertility.
This Mendelian randomization study, based on large-scale GWAS datasets, provides genetic evidence supporting a causal association between several autoimmune diseases and increased female infertility risk. These findings highlight the potential role of immune-mediated mechanisms in reproductive dysfunction and may inform future research into early interventions and fertility-preserving strategies in affected individuals.
不孕症在全球被视为一项重大的社会挑战。众多观察性研究记录了自身免疫性疾病（ADs）与女性不孕症之间的联系，但其潜在原因仍不清楚。本研究的主要目的是确定ADs与女性不孕症之间的因果关系。
我们评估了全基因组关联研究（GWAS）中关于常见自身免疫性疾病（系统性红斑狼疮（SLE）、类风湿关节炎（RA）、1型糖尿病（T1DM）、乳糜泻（CeD）、炎症性肠病（IBD）、强直性脊柱炎（AS）、克罗恩病（CD）、溃疡性结肠炎（UC）、银屑病）和女性不孕症的汇总统计数据。最初进行了两样本孟德尔随机化（MR）分析，以在发现和重复分析中确定与女性不孕症相关的因果自身免疫性疾病。
我们利用来自英国生物银行和芬兰基因库（或国际炎症性肠病遗传联盟（IIBDGC））的数据进行的两样本孟德尔随机化分析，为基因预测的类风湿关节炎（RA）、1型糖尿病（T1DM）、乳糜泻（CeD）和溃疡性结肠炎（UC）与女性不孕症风险增加之间的因果关联提供了证据。在不孕症的不同亚表型中均观察到了这些关联。
这项基于大规模GWAS数据集的孟德尔随机化研究提供了遗传证据，支持几种自身免疫性疾病与女性不孕症风险增加之间的因果关联。这些发现突出了免疫介导机制在生殖功能障碍中的潜在作用，并可能为未来针对受影响个体的早期干预和生育保护策略的研究提供参考。
