Immunoreactive erythropoietin concentrations in fetal and neonatal rats and the effects of hypoxia

Immunoreactive erythropoietin (Ep) was measured in normoxic and hypoxic (0.5 atm; 18 hours) fetal rats from day 14 to day 21 of gestation and in neonatal rats from birth to weaning, and was compared to the adult rat. Amniotic fluid (AF) Ep was approximately 100 mU/mL on day 14 and 15, and decreased to 20 mU/mL on day 20, with no difference between the hypoxic and normoxic mothers. Only on day 21 did the Ep in the AF increase slightly in the hypoxic group, while the Ep in the control group continued to fall to 15 mU/mL on day 21, the last day of pregnancy. Before day 17 of gestation the rat fetus appears to have hypoxia-independent, extrahepatic Ep available which is followed by hepatic and renal Ep production, both of which become sensitive to maternal hypoxia during the last days of pregnancy. In the neonatal rat plasma and tissue, Ep levels varied greatly during the first three weeks of life regardless of whether the animals were hypoxic or not. With the exception of the first and ninth days of life, circulating Ep levels were higher than adult levels in normal newborn rats. Neonatal rats responded to hypoxia with increasing Ep levels, and the response increased with age such that during the third week of life the plasma Ep levels were significantly higher than in adult hypoxic rats. No sex difference in male and female response to hypoxia could be documented until sexual maturity (day 42). In the normoxic neonatal rat more Ep originated from the liver than the kidneys until day 10, while under hypoxic conditions the switch occurred as early as two days after birth.