Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
Pediatr Res. 2018 Dec;84(6):807-812. doi: 10.1038/s41390-018-0054-4. Epub 2018 Jun 12.
Fetal erythropoietin (EPO), in addition to regulating erythropoiesis, has also tissue-protective properties based on its anti-inflammatory, anti-apoptotic, antioxidant, and neurotrophic effects. Notably, EPO concentrations needed for tissue protection are 100-1000 times higher than concentrations needed for regulating erythropoiesis. This dual effect of EPO is based on EPO-receptor (EPO-R) isoforms, which differ structurally and functionally. We hypothesize in this Integrated Mechanism Review that during severe fetal hypoxia the observed, but poorly understood, marked increases of fetal plasma EPO concentrations occur to protect the brain, heart, and other vital fetal organs. We further hypothesize that the concurrent marked increases of EPO in the amniotic fluid during fetal hypoxia, occur to protect newborn infants from necrotizing enterocolitis. This review presents experimental and clinical evidence in support of these hypotheses and points out unknown or poorly understood functions of EPO in the fetus. If these novel hypotheses are correct, the importance of fetal EPO as an antenatal hypoxia biomarker will become apparent. It will also likely point the way to important diagnostic and therapeutic fetal and neonatal interventions.
胎儿促红细胞生成素 (EPO) 除了调节红细胞生成外，还具有组织保护特性，这是基于其抗炎、抗凋亡、抗氧化和神经营养作用。值得注意的是，EPO 发挥组织保护作用所需的浓度比调节红细胞生成所需的浓度高 100-1000 倍。EPO 的这种双重作用基于 EPO 受体 (EPO-R) 异构体，这些异构体在结构和功能上存在差异。在本综合机制综述中，我们假设在严重胎儿缺氧期间，观察到但尚未充分了解的胎儿血浆 EPO 浓度显著增加，是为了保护大脑、心脏和其他重要胎儿器官。我们进一步假设，胎儿缺氧期间羊水 EPO 浓度的同时显著增加，是为了保护新生儿免受坏死性小肠结肠炎的影响。本综述提供了支持这些假设的实验和临床证据，并指出了 EPO 在胎儿中的未知或了解甚少的功能。如果这些新的假设是正确的，那么胎儿 EPO 作为产前缺氧生物标志物的重要性将变得明显。它还可能为重要的胎儿和新生儿干预措施指明方向，用于诊断和治疗。
