由基因组不稳定引起的炎症导致的雌性胚胎死亡
Adrian J McNairn1, Chen-Hua Chuang2, Jordana C Bloom1
1Cornell University College of Veterinary Medicine, Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
Nature
|February 22, 2019
概括
基因组不稳定性导致雌性小鼠的胚胎死亡率高于雄性. 和抗炎药物通过减少与DNA复制损伤相关的炎症来保护女性胚胎.
科学领域:
- 发育生物学
- 遗传学
- 免疫学
背景情况:
- 已知基因组不稳定会影响细胞的衰老和炎症.
- 它对胚胎发育,即快速细胞增殖阶段的影响尚不清楚.
- 小染色体维护 (MCM) 复合体 (MCM2-7) 对于DNA复制至关重要.
研究的目的:
- 研究小鼠胚胎发育过程中基因组不稳定的作用.
- 确定与MCM突变相关的胚胎死亡率的性别偏差原因.
- 探索潜在的保护机制对DNA复制诱导的炎症.
主要方法:
- 研究了MCM基因的突变,导致小鼠胚胎的基因组不稳定.
- 评估了男性与女性胚胎的胚胎死亡率.
- 研究性逆转,和抗炎药物 (ibuprofen) 的救援作用.
- 研究了Fancm基因突变和IL10受体缺陷的作用.
主要成果:
- 具有MCM突变的雌性胚胎比雄性胚胎更容易发生胚胎死亡.
- 这种性别偏见与"男性性"有关, 可以通过或性别逆转来挽救.
- 的保护作用与其抗炎性有关.
- 伊布洛芬拯救了具有MCM或Fancm突变的雌性胚胎,这表明炎症在复制压力中的作用.
- 在MCM突变中,IL10受体缺乏是合成致命的.
结论:
- 在复制过程中DNA受损会引发炎症,
- 男子胚胎受到内在的保护.
- 的抗炎作用是保护男性胚胎在发育过程中的关键.
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