妊娠期间DNA甲基化中的性别差异:大规模,交叉队列,多组织分析
Darina Czamara1, Linda Dieckmann2,3, Marius Lahti-Pulkkinen4,5,6
1Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany. darina@psych.mpg.de.
Cellular and molecular life sciences : CMLS
|April 10, 2024
概括
生物性别影响健康,胎盘DNA甲基化 (DNAm) 显示出显著的性别差异. 这些表观遗传变异,特别是女性较低的DNAm,可能会将胎盘发育与大脑功能联系起来.
科学领域:
- 生殖生物学和表观遗传学
- 发育生物学是发展生物学.
- 神经科学是一个神经科学.
背景情况:
- 生物性别显著影响生理系统,疾病易感性和治疗结果.
- 基于性别的差异在生命早期就显而易见,影响到怀孕和分娩.
- 胎盘表现出性别特异性激素和细胞因子的表达,这表明潜在的表观遗传调节.
研究的目的:
- 为了研究胎盘DNA甲基化 (DNAm) 的基于性别的差异.
- 为了确定与胎儿性别相关的特定差异甲基化探针 (DMPs).
- 探索与神经发育相关的这些性别差异化DNAm模式的功能影响.
主要方法:
- 在三个队伍中对胎盘DNAm进行元分析.
- 全表观基因组关联研究 (EWAS) 以确定性别-DMPs.
- 路径丰富,meQTL和PheWAS分析来解释DMP的功能.
- 交叉组织 (胎盘,胆囊取样本,带血) 和基因表达相关性.
主要成果:
- 在出生时胎盘中确定了10320个全表观基因组显著的性别DMP.
- 大多数DMP显示女性的DNAm水平较低.
- DMPs在神经发育路径中得到了丰富,并与meQTL和PheWAS相重叠.
- 早期胎盘和出生胎盘之间的效果大小中等相关性;与带血的相关性较弱.
- 胎盘中的性别差异基因表达不如DNAm差异那么明显.
结论:
- 胎盘DNAm表现出显著的性二态,与与胎儿性别相关的独特模式.
- 这些性别差异化的表观遗传标记可能在神经发育途径中发挥作用.
- 研究结果表明,胎盘表观遗传编程与大脑发育之间存在潜在的联系,受生物性别的影响.
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