27-基胆固醇通过激活PI3K/AKT/mTOR信号通路,通过激活胎盘发育期间的热囊细胞融合,从而抑制了热囊细胞融合
Xiaoyan Zhao1, Xiaxia Cai1, Haiyan Zhu2
1Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University, Beijing, 100069, People's Republic of China.
Archives of toxicology
|January 5, 2024
概括
27-胆固醇 (27-OHC) 抑制了必需的热囊细胞融合,影响胎盘发育和胎儿生长. 这通过激活PI3K/AKT/mTOR通路发生,揭示了与高胆固醇相关的妊娠并发症的机制.
科学领域:
- 生殖生物学和发育毒理学.
- 内分泌学和代谢障碍 代谢障碍
背景情况:
- 热囊细胞的同位素化对于胎盘发育至关重要;异常的融合与妊娠病理,如先孕症和子宫内生长限制有关.
- 27-胆固醇 (27-OHC),一种丰富的氧胆固醇,调解高胆固醇血相关疾病,但其在妊娠并发症中的作用尚不清楚.
- 妊娠期高胆固醇血症与早产和低出生体重等不良结果有关,需要机械理解.
研究的目的:
- 研究27-胆固醇 (27-OHC) 对热囊细胞融合和胎盘发育的影响.
- 阐明27-OHC影响 trofhoblast 融合和怀孕结果的潜在分子机制.
- 在小鼠模型中确定27-OHC暴露对胎儿生长和胎盘效率的影响.
主要方法:
- 在实验室研究中,使用初级人体热原体 (PHT) 和BeWo细胞治疗了不同度的27-OHC.
- 在体内实验中,CD-1小鼠接受了不同时间的27-OHC腹腔内注射.
- 热囊细胞融合的分析,PI3K/AKT/mTOR信号通路蛋白质表达,以及胎儿和胎盘参数的评估.
主要成果:
- 在体外模型和CD-1小鼠中,27-OHC显著抑制了 trofhoblast 细胞融合.
- 在PI3K/AKT/mTOR信号通路中,27-OHC上调调节了蛋白质;用LY294002抑制PI3K挽救了融合缺陷.
- 在体内,27-OHC治疗导致胎儿体重下降,胎盘效率降低,并抑制胎儿血管发育.
结论:
- 27-胆固醇 (27-OHC) 直接抑制热囊细胞融合,这是一项新发现,有助于了解妊娠病理.
- 27-OHC对热囊细胞融合的抑制作用是由PI3K/AKT/mTOR信号通路的激活介导的.
- 这项研究揭示了一种关键的机制,将孕产妇脂质不良症,特别是27-OHC升高,与通过胎盘发育受损的不良妊娠结果联系起来.
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