有机酸干扰了KGN中的类固醇生成 人类卵巢粒状细胞
Xiaotong Wang1, Elaine Lee1, Barbara F Hales1
1Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada.
Endocrinology
|June 8, 2023
概括
有机酸 (OPEs) 通过改变类固醇和胆固醇合成基因,破坏卵巢细胞中的雌激素产生. 这可能会对女性的生育能力和生殖产生负面影响.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 生殖生物学 生殖生物学
背景情况:
- 有机酸 (OPE) 是广泛使用的阻燃剂和增塑剂,在全球环境和人类样本中检测到.
- 之前的研究表明,OPE暴露可能会干扰女性性激素平衡和生殖健康.
研究的目的:
- 研究OPE对KGN卵巢颗粒细胞的类固醇功能的影响.
- 为了确定OPEs是否在类固醇和胆固醇生物合成途径中的基因表达失调.
主要方法:
- 在48小时内,KGN细胞被暴露在五种不同的OPE (TPHP,TMPP,IPPP,BPDP,TBOEP) 或BDE-47中,有或没有Bu2cAMP刺激.
- 测量了激素的产生 (孕激素和雌激素).
- 定量实时PCR (qRT-PCR) 评估了关键类固醇和胆固醇生物合成基因 (STAR,CYP11A1,CYP19A1,HSD3B2,NR5A1,HMGCR,SREBF2) 的表达.
主要成果:
- OPEs增加了基底孕激素和雌激素的产生,但抑制了Bu2cAMP刺激的合成.
- OPEs对类固醇生成基因 (STAR,CYP11A1,CYP19A1,HSD3B2,NR5A1) 的基底表达进行上调,并在刺激时对其表达进行下调.
- OPEs通过降低HMGCR和SREBF2表达的调节来抑制胆固醇生物合成;TBOEP显示的效果最小.
结论:
- OPEs通过改变参与类固醇和胆固醇代谢的基因的表达来破坏卵巢颗粒细胞中的类固醇生成.
- 这些细胞功能的干扰可能会对女性生殖健康产生不利影响.
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