The Causal Relationship Between Immune Cells and Infertility: A Mendelian Randomisation Study

IF 2.4 3区医学 Q3 IMMUNOLOGY American Journal of Reproductive Immunology Pub Date : 2024-09-25 DOI:10.1111/aji.13932

Dingchuan Peng, Wei Zhong, Yiran Wang, Yiyao Fu, Wei Shang

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Abstract

Objective

Infertility has emerged as a significant global public health concern, with a multitude of complex underlying causes. Epidemiological evidence indicates that immunological factors are significant contributors to the aetiology of infertility. However, previous studies on the relationship between immune inflammation and infertility have yielded inconclusive results.

Methods

Mendelian randomisation (MR) is an emerging statistical method that employs exposure-related genetic variation as an instrumental variable (IV) to infer causal relationships between immune cells and infertility by modelling the principle of random assignment in Mendelian genetics. In this study, MR was employed to assess the causal relationship between 731 immune cell signatures and infertility. The data utilized in this study were obtained from publicly available genome-wide association studies (GWAS) and validated IVs, which were employed to fulfil the essential assumptions of MR analysis.

Results

The Mendelian randomisation analysis revealed a total of 27 statistically significant immune cell phenotypes out of 731. The risk factor with the largest odds ratio (OR) was CD28⁻ CD25⁺⁺ CD8⁺ %T cell [OR, 1.21; 95% confidence interval (CI), 1.04–1.42], while the protective factor with the largest OR was activated and resting Treg AC (OR, 0.89; 95% CI, 0.82–0.97).

Conclusion

The present study has demonstrated a correlation between certain characteristics of immune cells and female infertility. These results provide clues for further research into the immune mechanisms of infertility and may inform the development of novel therapeutic strategies.

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免疫细胞与不孕不育之间的因果关系：孟德尔随机研究

不孕不育已成为全球公共卫生的一个重大问题，其根本原因错综复杂。流行病学证据表明，免疫因素是导致不孕症的重要原因。然而，以往关于免疫炎症与不孕不育之间关系的研究并没有得出结论。方法孟德尔随机化（Mendelian randomisation，MR）是一种新兴的统计方法，它采用与暴露相关的遗传变异作为工具变量（IV），通过模拟孟德尔遗传学中的随机分配原则来推断免疫细胞与不孕不育之间的因果关系。在本研究中，采用 MR 评估了 731 个免疫细胞特征与不孕不育之间的因果关系。本研究使用的数据来自公开的全基因组关联研究（GWAS）和经过验证的IVs，这些数据满足了MR分析的基本假设。结果孟德尔随机分析显示，在 731 种免疫细胞表型中，共有 27 种具有统计学意义。几率比（OR）最大的风险因素是 CD28- CD25++ CD8+ %T 细胞[OR，1.21；95% 置信区间（CI），1.04-1.42]，而几率比最大的保护因素是活化和静息 Treg AC（OR，0.89；95% CI，0.82-0.97）。结论本研究证明了免疫细胞的某些特征与女性不孕症之间的相关性。这些结果为进一步研究不孕症的免疫机制提供了线索，并可为开发新型治疗策略提供参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Reproductive Immunology 医学-免疫学

CiteScore

6.20

自引率

5.60%

发文量

314

审稿时长

2 months

期刊介绍： The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.