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低剂量暴露于微塑料会通过HDAC3缺陷延迟介质成熟

Qi Zhao^1,2, Ming Zong¹, Entong Song¹

¹Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China.

Science China. Life sciences

|February 20, 2025

概括

聚乙烯微塑料 (PSMPs) 通过损害卵细胞成熟而导致女性不孕. 这是由于HDAC3不足而发生的,导致代谢变化和异常的激素乙化,这表明HDAC3激活是潜在的治疗方法.

科学领域:

生殖毒理学生殖毒理学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
环境健康环境健康

背景情况:

微塑料 (MP) 与不孕症有关,但机制尚不清楚,特别是在慢性低剂量暴露时.
目前的理解严重依赖于急性MP暴露的动物模型.
调查环境污染物如MPs对生殖健康的影响至关重要.

研究的目的:

研究低剂量聚烯微塑料 (PSMP) 对女性生殖健康的影响.
为了阐明PSMP诱导的卵细胞介质成熟缺陷的潜在分子机制.
确定MP相关不孕症的潜在治疗点.

主要方法:

在体内和体外暴露卵细胞PSMPs.
对卵细胞中介成熟的分析.
评估细胞代谢途径和基因素乙化 (H4K16).
使用HDAC3抑制剂和HDAC3.3过度表达的药理学操纵.

主要成果:

低剂量的PSMP暴露导致了女性显著的生殖异常,特别是卵细胞介质成熟缺陷.
暴露于PSMP导致细胞代谢过度活化,HDACs不足以及卵细胞中的H4K16过化.
抑制HDAC3重现了这些缺陷,而HDAC3过度表达则挽救了PSMP诱导的成熟缺陷.

结论:

由PSMP引起的卵细胞成熟缺陷与HDAC3缺乏直接相关.
在对微塑料暴露的反应中,HDAC3在调节卵细胞成熟方面发挥着至关重要的作用.
激活或补充HDAC3可能为MP诱导的不孕症妇女提供治疗策略.

关键词:

在H4K16ac中使用.这就是HDACs.细胞代谢的细胞代谢介质性成熟的过程聚乙烯微塑料的微塑料

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