Xie Yafei, Zhang Zelin, Zhao Yuanyuan, Zhang Jiali, Yin Qiaozhi
School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People's Republic of China.
Int J Womens Health. 2025 Aug 7;17:2451-2463. doi: 10.2147/IJWH.S534136. eCollection 2025.
It has been noted that plasma lipid levels are closely associated with polycystic ovary syndrome (PCOS). Immune cells have also been recognized as critical indicators for evaluating the impact of lipids on disease progression. However, there is still a lack of conclusive causal evidence as to whether immune cells mediate the relationship between lipids and PCOS.
This study used a two-step two-sample Mendelian randomisation (TSMR) analysis to explore the causal relationship between plasma lipid groups and PCOS, and the mediating role of immune cells in this relationship. Transcriptome analysis was used to further explore the relationship between lipid metabolism, immunity, and PCOS.
The inverse variance weighted (IVW) method and Bayesian weighted Mendelian randomized (BWMR) method identified six plasma lipid groups that exhibited causal effects on PCOS, with no evidence of reverse causality. Eighteen immune cell traits are strongly associated with PCOS. TSMR analysis identified SSC-A on CD4+ as the key factor mediating the causal association of PC (0:18:1_20:4) and PI (18:1_18:2) with PCOS, with mediating effects of -0.003 (95% CI [-0.017, 0.012]) and 0.003 (95% CI [-0.021, 0.026]), respectively. Functional enrichment analysis revealed that PCOS was strongly associated with numerous immune pathways. Immune infiltration evaluation results indicated significant disparities in the distribution of a substantial number of immune cells, especially for all types of CD4+ T cells. Furthermore, Metabolic inference analysis revealed that fatty acid biosynthesis is closely related to PCOS.
Our results provide genetic and transcriptomic evidence substantiating the potential relationship between lipids, immune cells, and PCOS. CD4+ T cells might be key mediators in the causal association between lipids and PCOS. Comprehending this relationship could enhance treatment and prevention strategies for PCOS through the comprehensive management of lipid irregularities. Further experimental studies are required to elucidate the detailed mechanisms involved in this relationship.
已有研究指出，血浆脂质水平与多囊卵巢综合征（PCOS）密切相关。免疫细胞也被认为是评估脂质对疾病进展影响的关键指标。然而，关于免疫细胞是否介导脂质与PCOS之间的关系，仍缺乏确凿的因果证据。
本研究采用两步两样本孟德尔随机化（TSMR）分析，以探讨血浆脂质组与PCOS之间的因果关系，以及免疫细胞在这种关系中的中介作用。转录组分析用于进一步探索脂质代谢、免疫与PCOS之间的关系。
逆方差加权（IVW）法和贝叶斯加权孟德尔随机化（BWMR）法确定了六个对PCOS有因果效应的血浆脂质组，且无反向因果关系的证据。18种免疫细胞特征与PCOS密切相关。TSMR分析确定CD4+上的SSC-A是介导PC（0:18:1_20:4）和PI（18:1_18:2）与PCOS因果关联的关键因素，中介效应分别为-0.003（95%CI[-0.017,0.012]）和0.003（95%CI[-0.021,0.026]）。功能富集分析表明，PCOS与众多免疫途径密切相关。免疫浸润评估结果表明，大量免疫细胞的分布存在显著差异，尤其是所有类型的CD4+T细胞。此外，代谢推断分析表明脂肪酸生物合成与PCOS密切相关。
我们的结果提供了遗传和转录组学证据，证实了脂质、免疫细胞与PCOS之间的潜在关系。CD4+T细胞可能是脂质与PCOS因果关联的关键中介。了解这种关系可以通过全面管理脂质异常来加强PCOS的治疗和预防策略。需要进一步的实验研究来阐明这种关系中涉及的详细机制。
