双甲暴露通过抑制PCBP2表达来降低精子生产和男性生育能力
Yuming Cao1, Jinfeng Xu1, Jie Liu1
1Department of Obstetrics and Gynecology, Perinatal Medical Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52 Meihua East Road, Zhuhai, Guangdong, People's Republic of China.
Environmental science and pollution research international
|November 20, 2023
概括
在雄性小鼠中,双甲 (BPA) 暴露减少了精子数量和形态受损. BPA通过表观遗传抑制关键基因表达来破坏精子细胞的发育,影响男性生育能力.
科学领域:
- 环境科学 环境科学
- 生殖生物学 生殖生物学
- 毒理学 毒理学 毒理学
背景情况:
- 双A (BPA) 是一种环境内分泌干扰物,可疑对生殖有不良影响.
- 之前对BPA对生育能力的影响的研究已经产生了相互矛盾的结果,而精确的机制仍然不清楚.
研究的目的:
- 调查BPA暴露对雄性小鼠生殖参数的影响.
- 阐明BPA损害精子生成的潜在分子机制,包括基因表达和表观遗传修饰.
主要方法:
- 雄性小鼠被口服暴露于BPA (50 mg/kg/d) 或玉米油28天.
- 评估精子数量,形态,受精能力,血清丸激素水平,DNA损伤和亡.
- 利用RNA测序和RNA干扰来识别和验证受BPA影响的基因和调节通路 (EZH2/H3K27me3,PCBP2).
主要成果:
- 暴露于BPA显著降低了精子数量和受损的精子形态.
- 在暴露于BPA的小鼠中观察到血清丸激素水平降低和受精效率降低.
- BPA通过EZH2/H3K27me3表观遗传修饰抑制了PCBP2表达,影响了精子的发育.
结论:
- 暴露于BPA会损害雄性小鼠的生殖健康,包括精子生成和生育能力.
- 像PCBP2这样的关键基因的表观遗传修饰是BPA诱导的生殖毒性的重要机制.
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