Davis Lowell E, Widness John A, Brace Robert A
Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR, USA.
Am J Obstet Gynecol. 2003 Dec;189(6):1764-70. doi: 10.1016/s0002-9378(03)00874-3.
The source of the erythropoietin (EPO) that circulates in the fetus is unknown although it is known that EPO does not cross the placenta and that fetal kidneys, liver, and placenta express the EPO gene. This study tested to what extent in vivo EPO secretion by the fetal kidneys and placenta can be demonstrated under normoxic and hypoxic conditions.
Renal arterial and venous EPO concentrations were determined in eight late-gestation chronically catheterized fetal sheep made progressively anemic by exchange transfusion with saline solution over 5 to 8 days. In a separate additional series of experiments, umbilical arterial and venous EPO concentrations were determined in nine normoxic fetuses and in nine fetuses subjected to 12 hours of hypoxia induced by lowering maternal-inspired oxygen content. Organ secretion rates were calculated as the product of plasma flow rate and the arteriovenous concentration differences.
Renal vein plasma EPO concentration was higher than the arterial concentration in 36 of 40 paired samples (P<.0001) by 16.3%+/-2.7% (mean+/-SE). This difference was concentration independent over a range of 12 to 4100 mU/mL. Renal EPO secretion rates were variable and averaged 155+/-105 mU/min when hematocrit was 31.3%+/-1.6% (n=5) and 1124+/-300 mU/min post-exchange transfusion when hematocrit was 15.6%+/-0.8% (n=12). In contrast, umbilical venous and arterial EPO concentrations (range 9-35 mU/mL), although highly correlated (r=0.94), were not different during normoxia (Po(2)=21.6+/-0.5 mm Hg, n=9). Under hypoxic conditions (Po(2)=15.6+/-0.4 mm Hg, n=9), umbilical vein EPO concentration (range 151-1245 mU/mL) was higher than arterial concentration (range 140-951 mU/mL) in eight of nine paired samples by 13.6%+/-3.3% (P<.01). Under these conditions, estimated umbilical EPO secretion rate was 27,900+/-11,500 mU/min.
Under nonanemic, normoxic basal conditions, the kidneys secreted EPO into the fetal circulation, whereas secretion by the placenta was not demonstrated. In the phlebotomy-induced fetal anemia experiments, the kidney demonstrated marked, progressive increases in the rate of EPO production. Similarly, in the fetal hypoxemia experiments, the placenta demonstrated progressive increases--albeit an order of magnitude greater than the kidneys--in EPO production rate. As an extension of these findings, we speculate that the hypoproliferative neonatal anemia that invariably occurs in the early weeks after birth is in part the result of loss of EPO production by the placenta.
尽管已知促红细胞生成素（EPO）不能穿过胎盘，且胎儿肾脏、肝脏和胎盘表达EPO基因，但循环于胎儿体内的EPO来源尚不清楚。本研究旨在检测在常氧和低氧条件下，胎儿肾脏和胎盘在体内分泌EPO的程度。
对8只妊娠晚期长期插管的胎羊进行研究，通过在5至8天内用盐溶液进行换血使其逐渐贫血，测定其肾动脉和静脉的EPO浓度。在另一系列单独的实验中，测定9只常氧胎儿和9只因降低母体吸氧含量而经历12小时缺氧的胎儿的脐动脉和静脉EPO浓度。器官分泌率通过血浆流速与动静脉浓度差的乘积计算得出。
在40对配对样本中，36对样本的肾静脉血浆EPO浓度高于动脉浓度（P<0.0001），高出16.3%±2.7%（平均值±标准误）。在12至4100 mU/mL的范围内，这种差异与浓度无关。当血细胞比容为31.3%±1.6%（n = 5）时，肾脏EPO分泌率变化不定，平均为155±105 mU/分钟；换血后血细胞比容为15.6%±0.8%（n = 12）时，分泌率为1124±300 mU/分钟。相比之下，脐静脉和动脉EPO浓度（范围为9 - 35 mU/mL）虽然高度相关（r = 0.94），但在常氧状态下（Po₂ = 21.6±0.5 mmHg，n = 9）并无差异。在低氧条件下（Po₂ = 15.6±0.4 mmHg，n = 9），9对配对样本中有8对样本的脐静脉EPO浓度（范围为|51 - 1245 mU/mL）高于动脉浓度（范围为140 - 951 mU/mL），高出13.6%±3.3%（P<0.01）。在这些条件下，估计脐部EPO分泌率为27,900±11,500 mU/分钟。
在非贫血、常氧基础条件下，肾脏向胎儿循环分泌EPO，而未证实胎盘有分泌。在放血诱导的胎儿贫血实验中，肾脏EPO产生速率显著且逐渐增加。同样，在胎儿低氧血症实验中，胎盘EPO产生速率也逐渐增加——尽管比肾脏高一个数量级。作为这些发现的延伸，我们推测出生后早期必然发生的低增生性新生儿贫血部分是由于胎盘EPO产生丧失所致。
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