Table1_Male infertility risk and plasma lipidome: a Mendelian randomization study.xls

BackgroundIn recent years, the decline in sperm quality in men has become a global trend. There is a close relationship between sperm quality and pregnancy outcome. There is a large body of literature supporting the role of plasma lipidome in male infertility, while the complex mechanisms between them and male infertility are still less clear. Systematic study of the causal relationship between plasma lipidome and MI can help to provide new therapeutic ideas and targets for male infertility.
MethodsIn this study, we used a two-sample Mendelian randomization analysis based on Genome-wide association studies pooled data of 179 causal relationships between plasma lipidome and male infertility. We used employed the inverse variance weighted method as the main analysis to assess causality between exposure and outcome, in addition to MR-Egger, Weighted median as complementary methods, and tests for multiplicity and heterogeneity.
ResultsWe identified 13 plasma lipidome comprising 4 types of plasma lipidome that were associated with male infertility. Among these, 9 plasma lipidome were found to be protective factors, while 4 were risk factors. Notably, the largest proportion of these plasma lipidome were triglyceride types, with Sphingomyelin (d40:1) exhibiting the strongest association with male infertility.
ConclusionThese findings contribute to the current better understanding of male infertility and provide new perspectives on the underlying etiology of male infertility as well as prevention and treatment strategies. In addition, clinical trial validation is needed to assess the potential of these plasma lipidome as biomarkers.

研究背景
近年来，男性精子质量下降已成为全球性公共卫生趋势。精子质量与妊娠结局密切相关。已有大量文献证实血浆脂质组（plasma lipidome）在男性不育（male infertility）中的致病作用，但二者与男性不育之间的复杂调控机制仍不甚明晰。系统探究血浆脂质组与男性不育的因果关联，可为男性不育的临床治疗提供全新思路与潜在靶点。

研究方法
本研究基于涵盖179对血浆脂质组与男性不育因果关联的全基因组关联研究汇总数据，开展两样本孟德尔随机化（Mendelian randomization, MR）分析。本研究以逆方差加权法作为核心分析手段，评估暴露因素与结局间的因果关联；同时辅以MR-Egger法、加权中位数法，并进行多重检验与异质性检验。

研究结果
本研究共筛选出与男性不育相关的13种血浆脂质组分，涵盖4大类血浆脂质。其中9种为保护性因素，剩余4种为风险因素。值得注意的是，此类脂质组分中占比最高的为甘油三酯类，而鞘磷脂（Sphingomyelin, d40:1）与男性不育的关联强度最高。

研究结论
本研究结果有助于进一步加深对男性不育的认知，为阐明男性不育的潜在病因及制定防治策略提供了全新视角。此外，尚需开展临床试验验证，以评估此类血浆脂质组分作为生物标志物的应用潜力。