Sources of amniotic fluid erythropoietin during normoxia and hypoxia in fetal sheep

Robert A. Brace, Cecilia Cheung, Lowell Davis, Robert Gagnon, Richard Harding, John A. Widness

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: Erythropoietin is present in human amniotic fluid and has been suggested as a marker of fetal hypoxia. The objectives of the present study were to determine whether erythropoietin is present in ovine amniotic fluid, fetal urine, and/or lung liquid and whether concentrations in these compartments change in parallel with endogenous fetal plasma erythropoietin concentration when the latter is increased experimentally. Study design: In late gestation chronically catheterized fetal sheep, samples of amniotic fluid and plasma, urine and plasma, lung liquid, amniotic fluid, and plasma were collected before and up to 7 days after induction of 4 types of fetal hypoxia: (1) acute anemic hypoxia that was induced by a single fetal hemorrhage, (2) progressive anemic hypoxia that was induced by daily exchange transfusion, (3) acute hypoxic hypoxia that was induced by the reduction of maternal inspired oxygen content, or (4) chronic placental insufficiency that was induced by daily umbilicoplacental embolization for 4 days. Erythropoietin concentrations were determined by radioimmunoassay. Statistical testing included analysis of variance and least squares regression. Results: Under basal, nonhypoxic conditions, amniotic fluid erythropoietin concentration averaged 33.2% ± 1.6% (SE) of fetal plasma erythropoietin concentration, and basal fetal urine and lung liquid erythropoietin concentrations ranged from low (2 = 6.7%; P = .0027; n = 132). Amniotic fluid erythropoietin concentration approximately doubled after 12 hours of severe hypoxic hypoxia or after 24 hours of embolization-induced severe hypoxia but was unchanged after 12 hours of mild-moderate hypoxic hypoxia or 24 hours of anemic hypoxia. Concomitant fetal plasma erythropoietin concentrations increased to 28.1 ± 5.3, 12.5 ± 2.7, 10.8 ± 4.6, and 10.0 ± 1.3 times basal values, respectively. During progressive fetal anemia, urinary erythropoietin concentration increased almost 10-fold (P = .0023) but remained a small fraction (3.7% ± 0.4%) of plasma concentration; at 12 hours of hypoxic hypoxia, lung liquid erythropoietin concentration did not vary with the severity of the hypoxia and remained low relative to plasma concentration (4.2% ± 2.1%). Conclusion: Erythropoietin is present in ovine amniotic fluid, urine, and lung liquid. With only 3 potential sources, the fetal membranes appear to be the primary source of amniotic fluid erythropoietin in the nonhypoxic ovine fetus because basal urine and lung liquid erythropoietin concentrations are much lower than amniotic fluid concentrations. Although unchanged during mild-to-moderate fetal hypoxia, amniotic fluid erythropoietin concentration increases modestly during severe fetal hypoxia. In sheep, fetal urinary erythropoietin may contribute to this rise in amniotic fluid erythropoietin concentration during severe hypoxia, because fetal urinary and plasma concentrations increase in parallel during anemia.

Original languageEnglish (US)
Pages (from-to)246-254
Number of pages9
JournalAmerican Journal of Obstetrics and Gynecology
Volume195
Issue number1
DOIs
StatePublished - Jul 2006

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Fetal Hypoxia
Amniotic Fluid
Erythropoietin
Sheep
Lung
Urine
Anemia
Placental Insufficiency
Hypoxia
Extraembryonic Membranes

Keywords

  • Amniotic fluid
  • Erythropoietin
  • Fetus
  • Hypoxia
  • Intramembranous transport
  • Plasma
  • Sheep

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Sources of amniotic fluid erythropoietin during normoxia and hypoxia in fetal sheep. / Brace, Robert A.; Cheung, Cecilia; Davis, Lowell; Gagnon, Robert; Harding, Richard; Widness, John A.

In: American Journal of Obstetrics and Gynecology, Vol. 195, No. 1, 07.2006, p. 246-254.

Research output: Contribution to journalArticle

Brace, Robert A. ; Cheung, Cecilia ; Davis, Lowell ; Gagnon, Robert ; Harding, Richard ; Widness, John A. / Sources of amniotic fluid erythropoietin during normoxia and hypoxia in fetal sheep. In: American Journal of Obstetrics and Gynecology. 2006 ; Vol. 195, No. 1. pp. 246-254.
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abstract = "Objective: Erythropoietin is present in human amniotic fluid and has been suggested as a marker of fetal hypoxia. The objectives of the present study were to determine whether erythropoietin is present in ovine amniotic fluid, fetal urine, and/or lung liquid and whether concentrations in these compartments change in parallel with endogenous fetal plasma erythropoietin concentration when the latter is increased experimentally. Study design: In late gestation chronically catheterized fetal sheep, samples of amniotic fluid and plasma, urine and plasma, lung liquid, amniotic fluid, and plasma were collected before and up to 7 days after induction of 4 types of fetal hypoxia: (1) acute anemic hypoxia that was induced by a single fetal hemorrhage, (2) progressive anemic hypoxia that was induced by daily exchange transfusion, (3) acute hypoxic hypoxia that was induced by the reduction of maternal inspired oxygen content, or (4) chronic placental insufficiency that was induced by daily umbilicoplacental embolization for 4 days. Erythropoietin concentrations were determined by radioimmunoassay. Statistical testing included analysis of variance and least squares regression. Results: Under basal, nonhypoxic conditions, amniotic fluid erythropoietin concentration averaged 33.2{\%} ± 1.6{\%} (SE) of fetal plasma erythropoietin concentration, and basal fetal urine and lung liquid erythropoietin concentrations ranged from low (2 = 6.7{\%}; P = .0027; n = 132). Amniotic fluid erythropoietin concentration approximately doubled after 12 hours of severe hypoxic hypoxia or after 24 hours of embolization-induced severe hypoxia but was unchanged after 12 hours of mild-moderate hypoxic hypoxia or 24 hours of anemic hypoxia. Concomitant fetal plasma erythropoietin concentrations increased to 28.1 ± 5.3, 12.5 ± 2.7, 10.8 ± 4.6, and 10.0 ± 1.3 times basal values, respectively. During progressive fetal anemia, urinary erythropoietin concentration increased almost 10-fold (P = .0023) but remained a small fraction (3.7{\%} ± 0.4{\%}) of plasma concentration; at 12 hours of hypoxic hypoxia, lung liquid erythropoietin concentration did not vary with the severity of the hypoxia and remained low relative to plasma concentration (4.2{\%} ± 2.1{\%}). Conclusion: Erythropoietin is present in ovine amniotic fluid, urine, and lung liquid. With only 3 potential sources, the fetal membranes appear to be the primary source of amniotic fluid erythropoietin in the nonhypoxic ovine fetus because basal urine and lung liquid erythropoietin concentrations are much lower than amniotic fluid concentrations. Although unchanged during mild-to-moderate fetal hypoxia, amniotic fluid erythropoietin concentration increases modestly during severe fetal hypoxia. In sheep, fetal urinary erythropoietin may contribute to this rise in amniotic fluid erythropoietin concentration during severe hypoxia, because fetal urinary and plasma concentrations increase in parallel during anemia.",
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TY - JOUR

T1 - Sources of amniotic fluid erythropoietin during normoxia and hypoxia in fetal sheep

AU - Brace, Robert A.

AU - Cheung, Cecilia

AU - Davis, Lowell

AU - Gagnon, Robert

AU - Harding, Richard

AU - Widness, John A.

PY - 2006/7

Y1 - 2006/7

N2 - Objective: Erythropoietin is present in human amniotic fluid and has been suggested as a marker of fetal hypoxia. The objectives of the present study were to determine whether erythropoietin is present in ovine amniotic fluid, fetal urine, and/or lung liquid and whether concentrations in these compartments change in parallel with endogenous fetal plasma erythropoietin concentration when the latter is increased experimentally. Study design: In late gestation chronically catheterized fetal sheep, samples of amniotic fluid and plasma, urine and plasma, lung liquid, amniotic fluid, and plasma were collected before and up to 7 days after induction of 4 types of fetal hypoxia: (1) acute anemic hypoxia that was induced by a single fetal hemorrhage, (2) progressive anemic hypoxia that was induced by daily exchange transfusion, (3) acute hypoxic hypoxia that was induced by the reduction of maternal inspired oxygen content, or (4) chronic placental insufficiency that was induced by daily umbilicoplacental embolization for 4 days. Erythropoietin concentrations were determined by radioimmunoassay. Statistical testing included analysis of variance and least squares regression. Results: Under basal, nonhypoxic conditions, amniotic fluid erythropoietin concentration averaged 33.2% ± 1.6% (SE) of fetal plasma erythropoietin concentration, and basal fetal urine and lung liquid erythropoietin concentrations ranged from low (2 = 6.7%; P = .0027; n = 132). Amniotic fluid erythropoietin concentration approximately doubled after 12 hours of severe hypoxic hypoxia or after 24 hours of embolization-induced severe hypoxia but was unchanged after 12 hours of mild-moderate hypoxic hypoxia or 24 hours of anemic hypoxia. Concomitant fetal plasma erythropoietin concentrations increased to 28.1 ± 5.3, 12.5 ± 2.7, 10.8 ± 4.6, and 10.0 ± 1.3 times basal values, respectively. During progressive fetal anemia, urinary erythropoietin concentration increased almost 10-fold (P = .0023) but remained a small fraction (3.7% ± 0.4%) of plasma concentration; at 12 hours of hypoxic hypoxia, lung liquid erythropoietin concentration did not vary with the severity of the hypoxia and remained low relative to plasma concentration (4.2% ± 2.1%). Conclusion: Erythropoietin is present in ovine amniotic fluid, urine, and lung liquid. With only 3 potential sources, the fetal membranes appear to be the primary source of amniotic fluid erythropoietin in the nonhypoxic ovine fetus because basal urine and lung liquid erythropoietin concentrations are much lower than amniotic fluid concentrations. Although unchanged during mild-to-moderate fetal hypoxia, amniotic fluid erythropoietin concentration increases modestly during severe fetal hypoxia. In sheep, fetal urinary erythropoietin may contribute to this rise in amniotic fluid erythropoietin concentration during severe hypoxia, because fetal urinary and plasma concentrations increase in parallel during anemia.

AB - Objective: Erythropoietin is present in human amniotic fluid and has been suggested as a marker of fetal hypoxia. The objectives of the present study were to determine whether erythropoietin is present in ovine amniotic fluid, fetal urine, and/or lung liquid and whether concentrations in these compartments change in parallel with endogenous fetal plasma erythropoietin concentration when the latter is increased experimentally. Study design: In late gestation chronically catheterized fetal sheep, samples of amniotic fluid and plasma, urine and plasma, lung liquid, amniotic fluid, and plasma were collected before and up to 7 days after induction of 4 types of fetal hypoxia: (1) acute anemic hypoxia that was induced by a single fetal hemorrhage, (2) progressive anemic hypoxia that was induced by daily exchange transfusion, (3) acute hypoxic hypoxia that was induced by the reduction of maternal inspired oxygen content, or (4) chronic placental insufficiency that was induced by daily umbilicoplacental embolization for 4 days. Erythropoietin concentrations were determined by radioimmunoassay. Statistical testing included analysis of variance and least squares regression. Results: Under basal, nonhypoxic conditions, amniotic fluid erythropoietin concentration averaged 33.2% ± 1.6% (SE) of fetal plasma erythropoietin concentration, and basal fetal urine and lung liquid erythropoietin concentrations ranged from low (2 = 6.7%; P = .0027; n = 132). Amniotic fluid erythropoietin concentration approximately doubled after 12 hours of severe hypoxic hypoxia or after 24 hours of embolization-induced severe hypoxia but was unchanged after 12 hours of mild-moderate hypoxic hypoxia or 24 hours of anemic hypoxia. Concomitant fetal plasma erythropoietin concentrations increased to 28.1 ± 5.3, 12.5 ± 2.7, 10.8 ± 4.6, and 10.0 ± 1.3 times basal values, respectively. During progressive fetal anemia, urinary erythropoietin concentration increased almost 10-fold (P = .0023) but remained a small fraction (3.7% ± 0.4%) of plasma concentration; at 12 hours of hypoxic hypoxia, lung liquid erythropoietin concentration did not vary with the severity of the hypoxia and remained low relative to plasma concentration (4.2% ± 2.1%). Conclusion: Erythropoietin is present in ovine amniotic fluid, urine, and lung liquid. With only 3 potential sources, the fetal membranes appear to be the primary source of amniotic fluid erythropoietin in the nonhypoxic ovine fetus because basal urine and lung liquid erythropoietin concentrations are much lower than amniotic fluid concentrations. Although unchanged during mild-to-moderate fetal hypoxia, amniotic fluid erythropoietin concentration increases modestly during severe fetal hypoxia. In sheep, fetal urinary erythropoietin may contribute to this rise in amniotic fluid erythropoietin concentration during severe hypoxia, because fetal urinary and plasma concentrations increase in parallel during anemia.

KW - Amniotic fluid

KW - Erythropoietin

KW - Fetus

KW - Hypoxia

KW - Intramembranous transport

KW - Plasma

KW - Sheep

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