Hypoxia induced activin secretion by the fetoplacental unit: differential responses related to gestation

BJOG. 2004 Dec;111(12):1346-52. doi: 10.1111/j.1471-0528.2004.00269.x.

Abstract

Objective: To determine whether activin A levels reflect oxygen availability in basal and hypoxic conditions in the late pregnant fetus and newborn lamb.

Design: In vivo animal experimental study.

Setting: Department of Physiology, Monash University.

Population: Chronically catheterised fetal sheep in late gestation.

Methods: Fetal hypoxia was induced at 125 (n = 4), 135 (n = 4) or 145 days ('term'; n = 3) gestational age by maternal nitrogen exposure, for 4 hours, during which maternal and fetal arterial, and amniotic fluid samples were collected. Lambs (age one, five and eight days; n = 3) were exposed to 1 hour of hypoxia via nitrogen exposure.

Main outcome measures: Activin A, prostaglandin E2 (PGE2) and cortisol were analysed in plasma and amniotic fluid, and whole blood was used to determine Pao2, Paco2, %O2, lactate and pH.

Results: Basal activin A concentrations in the fetal arterial circulation remained unchanged between 125 days (0.230 [0.10] ng/mL) and term (0.28 [0.10] ng/mL), as did fetal oxygen saturation (59.11% [4.74%] to 52.25% [4.84%]) and pH (7.35 [0.02] to 7.37 [0.02]). Moderate fetal hypoxia (50% fall in fetal arterial %O2) produced a significant increase in circulating activin A (2.05 [0.67] ng/mL) and a significant decrease in pH (7.27 [0.03]) at 125 days of gestation, however, at 135 and 145 days, activin A and pH remained unchanged. Fetal activin A concentration was significantly correlated with pH (P = 0.036) but not %O2 (P = 0.072). Hypoxia in the lambs did not alter circulating activin A.

Conclusions: In response to hypoxia, activin A is increased in the circulation of 125-day-old fetuses, but not in older fetuses. Fetal arterial activin A levels sensitively reflect pH but not oxygen saturation, with increasing activin A in conditions of metabolic acidosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / metabolism*
  • Animals
  • Animals, Newborn / metabolism*
  • Female
  • Fetal Hypoxia / metabolism*
  • Fetus / blood supply
  • Gestational Age
  • Inhibin-beta Subunits / metabolism*
  • Nitrogen / pharmacology
  • Oxygen / blood
  • Partial Pressure
  • Placenta / metabolism*
  • Pregnancy
  • Sheep

Substances

  • activin A
  • Activins
  • Inhibin-beta Subunits
  • Nitrogen
  • Oxygen