仅用孕激素避孕药增强ZBTB16水平诱导决定化和炎症
Sefa Arlier1, Umit A Kayisli1, Nihan Semerci1
1Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
International journal of molecular sciences
|July 14, 2023
概括
只有孕激素的避孕药会增加ZBTB16,这是一种与决定化相关的蛋白质. 这可能会导致异常的子宫出血,因为它会促进子宫内膜的炎症和血栓生成.
科学领域:
- 生殖内分泌学 生殖内分泌学
- 分子生物学分子生物学
- 妇科 妇科 妇科 妇科
背景情况:
- 长效可逆避孕药 (pLARCs) 与异常子宫出血 (AUB) 有关.
- 在PLARC使用者中,分离的人类子宫内膜层细胞 (HESC) 呈现脆弱的微血管和增加的组织因子,导致过多的血栓生成和AUB.
- ZBTB16 (含有16的指和BTB域) 是决定化的关键调节者,其表达是由像medroxyprogesterone acetate (MPA) 和etonogestrel (ETO) 等孕激素诱导的.
研究的目的:
- 调查ZBTB16在pLARC诱导的决策中的作用及其对AUB的贡献.
- 为了确定长时间通过PLARCs增强ZBTB16是否会在决定化的HESC中引发炎症反应和血栓生成.
主要方法:
- ZBTB16在女性和用孕激素治疗的几内亚猪的子宫内膜组织中的免疫染色.
- 定量PCR (qPCR) 和免疫血栓测量ZBTB16水平在各种孕激素治疗的培养HESC中.
- 评估MPA对葡萄糖皮质素受体沉默的HESC中ZBTB16的调控.
- 在HESC中过度表达ZBTB16,随后进行血栓治疗以评估炎症基因表达.
主要成果:
- 孕激素的使用 (MPA,ETO,levonorgestrel) 显著增加了HESC中的ZBTB16水平,MPA显示出最明显的效果.
- 由MPA诱导的ZBTB16表达取决于葡萄糖皮质体受体.
- 在HESC中ZBTB16的过度表达增加了益生素 (PRL),IGFBP1和组织因子 (F3) 的水平.
- ZBTB16过度表达放大了炎症基因IL-8和PTGS2.2的氨酸诱导的表达.
结论:
- 在决定化过程中,ZBTB16被上调,其通过PLARCs的长时间诱导通过增强的组织因子表达促进了血栓生成.
- 长期由PLARCs诱导ZBTB16,通过增加IL-8和PTGS2水平,促进决定化的HESCs的炎症,这可能解释了AUB.
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