Department of Physiology and Biophysics, Mississippi Center for Excellence in Perinatal Health, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, U.S.A.
Clin Sci (Lond). 2021 Oct 15;135(19):2307-2327. doi: 10.1042/CS20190070.
Preeclampsia (PE), the leading cause of maternal and fetal morbidity and mortality, is associated with poor fetal growth, intrauterine growth restriction (IUGR) and low birth weight (LBW). Offspring of women who had PE are at increased risk for cardiovascular (CV) disease later in life. However, the exact etiology of PE is unknown. Moreover, there are no effective interventions to treat PE or alleviate IUGR and the developmental origins of chronic disease in the offspring. The placenta is critical to fetal growth and development. Epigenetic regulatory processes such as histone modifications, microRNAs and DNA methylation play an important role in placental development including contributions to the regulation of trophoblast invasion and remodeling of the spiral arteries. Epigenetic processes that lead to changes in placental gene expression in PE mediate downstream effects that contribute to the development of placenta dysfunction, a critical mediator in the onset of PE, impaired fetal growth and IUGR. Therefore, this review will focus on epigenetic processes that contribute to the pathogenesis of PE and IUGR. Understanding the epigenetic mechanisms that contribute to normal placental development and the initiating events in PE may lead to novel therapeutic targets in PE that improve fetal growth and mitigate increased CV risk in the offspring.
子痫前期 (PE) 是孕产妇和胎儿发病率和死亡率的主要原因,与胎儿生长不良、宫内生长受限 (IUGR) 和低出生体重 (LBW) 有关。患有 PE 的女性的后代在以后的生活中患心血管 (CV) 疾病的风险增加。然而,PE 的确切病因尚不清楚。此外,目前尚无有效的干预措施来治疗 PE 或减轻 IUGR 和后代的慢性疾病的发育起源。胎盘对胎儿的生长和发育至关重要。表观遗传调节过程,如组蛋白修饰、microRNAs 和 DNA 甲基化,在胎盘发育中发挥着重要作用,包括对滋养细胞侵袭的调节和螺旋动脉重塑的贡献。导致 PE 中胎盘基因表达变化的表观遗传过程介导了导致胎盘功能障碍发展的下游效应,胎盘功能障碍是 PE 发病、胎儿生长不良和 IUGR 的关键介质。因此,本综述将重点关注导致 PE 和 IUGR 的表观遗传过程。了解有助于正常胎盘发育和 PE 起始事件的表观遗传机制,可能为 PE 提供新的治疗靶点,改善胎儿生长,减轻后代 CV 风险增加。