Zhao Xuanpeng, Meng Qingyan, Liu Shuang, Cheng Linqi, Li Baoshan, Cheng Dongkai
The Reproductive Laboratory of Shenyang Jinghua Hospital, Shenyang, Liaoning, China.
Department of Biotechnology, Shenyang Medical College, Shenyang, Liaoning, China.
Front Endocrinol (Lausanne). 2025 Mar 3;16:1523488. doi: 10.3389/fendo.2025.1523488. eCollection 2025.
Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder with a complex pathophysiology, affecting various aspects of women's health. Despite its widespread impact, the molecular basis and immunological aspects of PCOS remain insufficiently understood, limiting effective diagnosis and treatment strategies.
This study aims to elucidate the molecular and immunological landscape of PCOS by integrating gene expression profiles from healthy and PCOS-affected ovaries using both bulk and single-cell omics data, with the goal of constructing a comprehensive bioinformatics network that identifies potential biomarkers and therapeutic targets.
Leveraging publicly available omics datasets, we compared gene expression between healthy ovaries and those affected by PCOS through both bulk and single-cell analyses. Our approach focused on differential gene expression analysis, identification of distinct cell types and gene signatures in PCOS, construction of disease-specific gene expression modules, and mapping of cellular differentiation trajectories. Additionally, we examined the alterations in the immune microenvironment within PCOS to identify immune-related changes.
Our analyses uncovered unique molecular signatures and immune modules in PCOS, characterized by differential gene expression, the presence of unique cell types, and altered pathways compared to healthy controls. Notably, we identified a significant role for Complement Component 3 (C3) in mediating these changes. Through gene intervention targeting C3 in granulosa cells and functional studies examining the effects of secreted C3 protein on H295R cells, Low level C3 mitigated inflammatory responses, while excess C3 proved detrimental to cell growth.
Our integrative omics analysis provides new insights into the molecular and immunological underpinnings of PCOS, highlighting the role of C3 in the disease's pathogenesis. The identification of key molecular signatures and immune modules, including the involvement of C3, opens promising avenues for the development of novel diagnostic and therapeutic strategies for PCOS. These observations suggest that modulating C3 levels could have therapeutic implications for managing PCOS.
多囊卵巢综合征（PCOS）是一种常见的内分泌紊乱疾病，其病理生理机制复杂，影响女性健康的各个方面。尽管其影响广泛，但PCOS的分子基础和免疫学方面仍未得到充分了解，限制了有效的诊断和治疗策略。
本研究旨在通过整合来自健康卵巢和PCOS患者卵巢的基因表达谱，利用批量和单细胞组学数据，阐明PCOS的分子和免疫格局，目标是构建一个全面的生物信息学网络，以识别潜在的生物标志物和治疗靶点。
利用公开可用的组学数据集，我们通过批量和单细胞分析比较了健康卵巢与PCOS患者卵巢之间的基因表达。我们的方法侧重于差异基因表达分析、识别PCOS中不同的细胞类型和基因特征、构建疾病特异性基因表达模块以及绘制细胞分化轨迹。此外，我们研究了PCOS内免疫微环境的变化，以识别免疫相关变化。
我们的分析揭示了PCOS中独特的分子特征和免疫模块，其特征是与健康对照相比基因表达差异、独特细胞类型的存在以及通路改变。值得注意的是，我们确定补体成分3（C3）在介导这些变化中起重要作用。通过对颗粒细胞中C3进行基因干预以及研究分泌的C3蛋白对H295R细胞影响的功能研究，低水平的C3减轻了炎症反应，而过量的C3对细胞生长有害。
我们的综合组学分析为PCOS的分子和免疫基础提供了新的见解，突出了C3在疾病发病机制中的作用。关键分子特征和免疫模块的识别，包括C3的参与，为开发PCOS的新型诊断和治疗策略开辟了有前景的途径。这些观察结果表明，调节C3水平可能对PCOS的管理具有治疗意义。
