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

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.