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多层次的证据表明,KCTD15和FAM19A2是PFOA/PFOS介导的PCOS病原体的关键标

Yuxiao Jiang¹, Liying Ge², Shanshan Zhang³

¹Department of Physiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China; School of Life Sciences, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Ecotoxicology and environmental safety

|February 20, 2026

概括

这项研究通过识别KCTD15和FAM19A2作为关键基因,将每和多基物质 (PFAS) 暴露与多囊性卵巢综合征 (PCOS) 联系起来. 研究结果表明存在因果关系,并为环境生殖毒理学研究提供信息.

科学领域:

环境生殖毒理学环境生殖毒理学
内分泌学在内分泌学.
计算生物学计算生物学

背景情况:

多囊性卵巢综合征 (PCOS) 是一种常见的内分泌疾病,与环境因素,如和多基基物质 (PFAS) 相关.
PFAS-PCOS相互作用的分子机制及其对卵巢功能的影响尚不清楚.

研究的目的:

调查PFAS暴露和PCOS之间的关联背后的分子机制.
为了确定潜在的分子标和PFAS和PCOS之间的因果关系.

主要方法:

在吸收,新陈代谢,分布,分泌 (ADME) 分析和生物信息学分析 (GEO,GO,KEGG,WGCNA,LASSO) 中使用.
采用孟德尔随机化 (MR) 和分子动力学模拟 (MDS) 来评估因果关系和蛋白质相互作用.
对卵巢颗粒细胞 (GCs) 进行了体外实验,以评估PFAS暴露的影响.

主要成果:

确定了KCTD15和FAM19A2作为与PCOS和PFAS暴露相关的枢纽基因.
使用MR分析证实了KCTD15/FAM19A2和PCOS之间的因果关系.
证明PFAS暴露降低了GC活力,并在体外改变了KCTD15/FAM19A2表达,通过MDS观察到稳定的蛋白质结合.

结论:

KCTD15和FAM19A2被确定为潜在的关键基因,可以调解PCOS中PFAS暴露的影响.
提供了PFAS暴露和PCOS之间的因果关系的初步证据,突出了环境生殖毒理学的潜在目标.

关键词:

计算毒理学计算毒理学门德尔的随机化 (MR)分子动力学模拟 (MDS) 模拟和多醇基物质 (PFAS) 的使用.多囊性卵巢综合征 (PCOS) 是一种疾病.

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