调节20α-Hydroxysteroid脱酶的表达在预产期怀孕的人类子宫肌肉外活体
Marina Paul1,2,3, Anna Paredes Barreda2,4,5, Amy Gregson2,4,5
1School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, 2308, Australia.
Reproductive sciences (Thousand Oaks, Calif.)
|August 30, 2023
概括
基斯脱乙酶抑制剂阻断子宫肌肉中的孕失活,可能保持怀孕. 这项研究探讨了这些抑制剂如何影响AKR1C1表达,AKR1C1表达是分娩期间孕代谢中的关键酶.
科学领域:
- 生殖生物学 生殖生物学
- 分子内分泌学分子内分泌学
- 生物化学 生物化学
背景情况:
- 孕激素的退出对于期货劳动至关重要,部分由20α-hydroxysteroid脱酶 (20α-HSD) 通过子宫肌细胞中的AKR1C1基因表达介导.
- 长期分娩和早产时出现胆 ?? 膜炎时观察到AKR1C1表达的增加,这表明炎症的作用.
- 了解影响AKR1C1表达的因素对于管理早产和维持子宫静止至关重要.
研究的目的:
- 为了研究各种治疗剂对孕妇人体肌肉膜AKR1C1表达的作用,ex vivo.
- 确定基因组/蛋白脱乙酶抑制剂是否可以调节AKR1C1表达和孕激素失活.
- 探索潜在的治疗策略,以保护孕激素的抗分娩作用.
主要方法:
- 初级人类肌胎细胞被培养出活体48小时以模仿类似于分娩的条件.
- 细胞被用血清,前列腺素F2α,醇酸,机械拉伸,孕激素,cAMP和基因素脱乙酶抑制剂 (三氨酸A,氨酸,氨酸) 治疗.
- 量化了AKR1C1mRNA表达水平,以评估不同治疗的影响.
主要成果:
- 在培养过程中,AKR1C1表达的自发增加发生了,这表明过渡到类似于分娩的状态.
- 孕激素和cAMP进一步提高了AKR1C1的表达,而血清,PGF2α,PMA和拉伸没有显著的影响.
- 基斯脱乙酶抑制剂 (trichostatin A,SAHA,SBHA) 剂量取决于抑制培养诱导的AKR1C1上调.
结论:
- 通过HDAC抑制剂抑制基因组/蛋白质脱乙化,可以保持孕妇子宫中孕激素的抗炎和促静信号.
- 通过抑制AKR1C1来阻止孕激素的代谢失活,可以保持子宫静止.
- 基斯脱乙酶抑制剂代表着一种潜在的治疗类,用于保持或恢复孕妇子宫中的孕激素敏感性,从而有可能预防早产.
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